2,531 results match your criteria Cell stem cell[Journal]


Generation of Functional Liver Sinusoidal Endothelial Cells from Human Pluripotent Stem-Cell-Derived Venous Angioblasts.

Cell Stem Cell 2020 Jul 1. Epub 2020 Jul 1.

McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G1L7, Canada. Electronic address:

Liver sinusoidal endothelial cells (LSECs) form a highly specialized microvasculature that plays a critical role in liver function and disease. To better understand this role, we developed a strategy to generate LSECs from human pluripotent stem cells (hPSCs) by first optimizing the specification of arterial and venous angioblasts and derivative endothelial populations. Induction of a LSEC-like fate by hypoxia, cyclic AMP (cAMP) agonism, and transforming growth factor β (TGF-β) inhibition revealed that venous endothelial cells responded more rapidly and robustly than the arterial cells to upregulate LSEC markers and functions in vitro. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.007DOI Listing

From Skin to Brain: A Parkinson's Disease Patient Transplanted with His Own Cells.

Cell Stem Cell 2020 Jul;27(1):8-10

Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden. Electronic address:

In a pioneering study in New England Journal of Medicine, Schweitzer et al. (2020) report on a patient with Parkinson's disease who received a graft of dopamine neurons obtained from in vitro differentiated induced pluripotent stem cells, derived from the patient's own skin fibroblasts, showing the feasibility of autologous transplantation for dopamine cell replacement. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.008DOI Listing

Translational Research in Culture: AADAC, Diabetes, and Cardiovascular Disease.

Cell Stem Cell 2020 Jul;27(1):6-7

Department of Medicine/Divsion of Cardiology, and the Cardiovascular Research Center, New York University Grossman School of Medicine, New York, NY, USA. Electronic address:

Many type 2 diabetes patients develop cardiovascular disease (CVD) while some are protected. Toyohara et al. (2020) find that elevated arylacetamide deacetylase (AADAC) expression in vascular smooth muscle cells (dVSMCs) differentiated from patient-derived induced pluripotent stem cells is associated with cardioprotection. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.012DOI Listing

Wnt Activation and Reduced Cell-Cell Contact Synergistically Induce Massive Expansion of Functional Human iPSC-Derived Cardiomyocytes.

Cell Stem Cell 2020 Jul;27(1):50-63.e5

Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Modulating signaling pathways including Wnt and Hippo can induce cardiomyocyte proliferation in vivo. Applying these signaling modulators to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in vitro can expand CMs modestly (<5-fold). Here, we demonstrate massive expansion of hiPSC-CMs in vitro (i. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334437PMC

A Multiplex Human Pluripotent Stem Cell Platform Defines Molecular and Functional Subclasses of Autism-Related Genes.

Cell Stem Cell 2020 Jul;27(1):35-49.e6

The Center for Stem Cell Biology, Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY 10065, USA. Electronic address:

Autism is a clinically heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted interests, and repetitive behaviors. Despite significant advances in the genetics of autism, understanding how genetic changes perturb brain development and affect clinical symptoms remains elusive. Here, we present a multiplex human pluripotent stem cell (hPSC) platform, in which 30 isogenic disease lines are pooled in a single dish and differentiated into prefrontal cortex (PFC) lineages to efficiently test early-developmental hypotheses of autism. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.004DOI Listing

Rubbing Out Leukemia Stem Cells by Erasing the Eraser.

Cell Stem Cell 2020 Jul;27(1):3-5

Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address:

In this issue of Cell Stem Cell, Shen et al. (2020) and Wang et al. (2020) independently identify the essential function of mA demethylase ALKBH5 in maintaining myeloid leukemia stem cells. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.009DOI Listing

Cell-by-Cell Deconstruction of Stem Cell Niches.

Cell Stem Cell 2020 Jul;27(1):19-34

Department of Pathology and Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address:

Single-cell sequencing approaches offer exploration of tissue architecture at unprecedented resolution. These tools are especially powerful when deconvoluting highly specialized microenvironments, such as stem cell (SC) niches. Here, we review single-cell studies that map the cellular and transcriptional makeup of stem and progenitor niches and discuss how these high-resolution analyses fundamentally advance our understanding of how niche factors shape SC biology and activity. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.013DOI Listing

Is Obesity a Disease of Stem Cells?

Cell Stem Cell 2020 Jul;27(1):15-18

Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO, USA; Shriners Hospitals for Children, St. Louis, MO, USA; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO, USA. Electronic address:

Obesity disrupts physiological homeostasis and alters both systemic and local microenvironments that impact stem cell plasticity and impair regenerative capacity. We present growing evidence that reveals the bidirectionality of obesity-induced stem cell dysfunction and how the molecular changes in stem cells residing in obese environments may accelerate disease severity. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.019DOI Listing

Introductions to the Community: Early-Career Researchers in the Time of COVID-19.

Authors:

Cell Stem Cell 2020 07;27(1):13-14

COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331526PMC

Effects of Diet Choice on Stem Cell Function Necessitate Clarity in Selection and Reporting.

Cell Stem Cell 2020 Jul;27(1):11-12

Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. Electronic address:

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http://dx.doi.org/10.1016/j.stem.2020.06.014DOI Listing

One for All: A Pooled Approach to Classify Functional Impacts of Multiple Mutations.

Cell Stem Cell 2020 Jul;27(1):1-3

Child Study Center, Yale University, New Haven, CT 06520, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA. Electronic address:

Understanding common biological consequences of heterogenous mutations in complex polygenic conditions is challenging. In this issue of Cell Stem Cell, Cederquist et al. (2020) implement an in vitro pooled assay where 30 high-confidence ASD mutations engineered in subclones of a human pluripotent stem cell line can be investigated in parallel to reveal their effects on prefrontal cortex neurogenesis. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.016DOI Listing

Histone Acetyltransferase MOF Blocks Acquisition of Quiescence in Ground-State ESCs through Activating Fatty Acid Oxidation.

Cell Stem Cell 2020 Jun 24. Epub 2020 Jun 24.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address:

Self-renewing embryonic stem cells (ESCs) respond to environmental cues by exiting pluripotency or entering a quiescent state. The molecular basis underlying this fate choice remains unclear. Here, we show that histone acetyltransferase MOF plays a critical role in this process through directly activating fatty acid oxidation (FAO) in the ground-state ESCs. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.005DOI Listing

Intravital Imaging Reveals Motility of Adult Hematopoietic Stem Cells in the Bone Marrow Niche.

Cell Stem Cell 2020 Jun 18. Epub 2020 Jun 18.

Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA. Electronic address:

Adult mammalian hematopoietic stem cells (HSCs) reside in the bone marrow (BM) but can be mobilized into blood for use in transplantation. HSCs interact with BM niche cells that produce growth factor c-Kit ligand (Kitl/SCF) and chemokine CXCL12, and were thought to be static and sessile. We used two-photon laser scanning microscopy to visualize genetically labeled HSCs in the BM of live mice for several hours. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.003DOI Listing

A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.

Cell Stem Cell 2020 07 19;27(1):125-136.e7. Epub 2020 Jun 19.

Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA. Electronic address:

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. Read More

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http://dx.doi.org/10.1016/j.stem.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303620PMC

Overcoming Intrinsic H3K27me3 Imprinting Barriers Improves Post-implantation Development after Somatic Cell Nuclear Transfer.

Cell Stem Cell 2020 Jun 13. Epub 2020 Jun 13.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significant epigenetic barriers. Genomic imprinting is not generally regarded as such a barrier, although H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblast and extraembryonic tissues. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.014DOI Listing

Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity.

Cell Stem Cell 2020 Jun 10. Epub 2020 Jun 10.

Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address:

Cytokine-inducible SH2-containing protein (CIS; encoded by the gene CISH) is a key negative regulator of interleukin-15 (IL-15) signaling in natural killer (NK) cells. Here, we develop human CISH-knockout (CISH) NK cells using an induced pluripotent stem cell-derived NK cell (iPSC-NK cell) platform. CISH iPSC-NK cells demonstrate increased IL-15-mediated JAK-STAT signaling activity. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.008DOI Listing

Selective Translation of Cell Fate Regulators Mediates Tolerance to Broad Oncogenic Stress.

Cell Stem Cell 2020 Jun 2. Epub 2020 Jun 2.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address:

Human skin tolerates a surprisingly high burden of oncogenic lesions. Although adult epidermis can suppress the expansion of individual mutant clones, the mechanisms behind tolerance to oncogene activation across broader regions of tissue are unclear. Here, we uncover a dynamic translational mechanism that coordinates oncogenic HRAS-induced hyperproliferation with loss of progenitor self-renewal to restrain aberrant growth and tumorigenesis. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.007DOI Listing

Circadian Regulation of Adult Stem Cell Homeostasis and Aging.

Cell Stem Cell 2020 Jun;26(6):817-831

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain. Electronic address:

The circadian clock temporally organizes cellular physiology throughout the day, allowing daily environmental changes to be anticipated and potentially harmful physiologic processes to be temporally separated. By synchronizing all cells at the tissue level, the circadian clock ensures coherent temporal organismal physiology. Recent advances in our understanding of adult stem cell physiology suggest that aging and perturbations in circadian rhythmicity in stem cells are tightly intertwined. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.002DOI Listing

End Products of Telomere Research.

Cell Stem Cell 2020 Jun;26(6):804-805

Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia.

Most rare inherited telomere biology disorders and some common aging-related diseases are associated with shortened telomeres. In this issue of Cell Stem Cell, insights into one of the rarest genetic causes of these disorders led to the discovery (Nagpal et al., 2020) of small molecules that lengthen telomeres. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.006DOI Listing

Skinny Fat Cells Stimulate Wound Healing.

Cell Stem Cell 2020 Jun;26(6):801-803

Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

In this issue of Cell Stem Cell, Shook et al. (2020) reveal that dermal adipocytes regulate skin wound repair via release of fatty acids that promote macrophage recruitment and accelerated revascularization. Furthermore, mature dermal adipocytes dedifferentiate into migratory extracellularmatrix-producing myofibroblasts. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.021DOI Listing

There's No I in Team: Cellular Crosstalk Enhances In Vitro Cardiac Maturation.

Cell Stem Cell 2020 Jun;26(6):799-801

QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia. Electronic address:

Organoids and microtissues offer the unique opportunity to dissect cell-cell interactions in an organ-specific context without confounding effects of organ failure or organism viability. In a study in this issue of Cell Stem Cell, Giacomelli et al. (2020) add human cardiac fibroblasts into cardiac microtissues and reveal striking fibroblast-endothelial-cardiomyocyte crosstalk that promotes advanced cardiomyocyte maturation. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.009DOI Listing

Colon Cancer Heterogeneity: Welcome to the RiboZone.

Cell Stem Cell 2020 Jun;26(6):797-799

Discovery Oncology, Genentech Inc., South San Francisco, CA, USA. Electronic address:

In this issue of Cell Stem Cell, Morral et al. (2020) shed new light on the hierarchical organization of cells within colorectal cancer. They show that tumor cells at the apex of this hierarchy reside in particular tumor zones and possess high protein synthesis activity. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.005DOI Listing

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.

Cell Stem Cell 2020 Jun 27;26(6):832-844.e6. Epub 2020 May 27.

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. Electronic address:

CD133 marks self-renewing cancer stem cells (CSCs) in a variety of solid tumors, and CD133+ tumor-initiating cells are known markers of chemo- and radio-resistance in multiple aggressive cancers, including glioblastoma (GBM), that may drive intra-tumoral heterogeneity. Here, we report three immunotherapeutic modalities based on a human anti-CD133 antibody fragment that targets a unique epitope present in glycosylated and non-glycosylated CD133 and studied their effects on targeting CD133+ cells in patient-derived models of GBM. We generated an immunoglobulin G (IgG) (RW03-IgG), a dual-antigen T cell engager (DATE), and a CD133-specific chimeric antigen receptor T cell (CAR-T): CART133. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.008DOI Listing

Preying on Public Fears and Anxieties in a Pandemic: Businesses Selling Unproven and Unlicensed "Stem Cell Treatments" for COVID-19.

Authors:
Leigh Turner

Cell Stem Cell 2020 06 7;26(6):806-810. Epub 2020 May 7.

Center for Bioethics, School of Public Health, and College of Pharmacy, University of Minnesota, 410 Church Street SE, N520, Minneapolis, MN 55455, USA. Electronic address:

In the midst of a global public health emergency, some businesses are taking advantage of widespread fears by marketing purported stem cell treatments for COVID-19. Such businesses target prospective clients with misleading claims, expose patients to potentially risky stem cell-based products, and undermine efforts to develop evidence-based treatments for COVID-19. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203029PMC

Introductions to the Community: Early-Career Researchers in the Time of COVID-19.

Authors:

Cell Stem Cell 2020 06 20;26(6):815-816. Epub 2020 May 20.

COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237914PMC

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease.

Cell Stem Cell 2020 Jun 26;26(6):862-879.e11. Epub 2020 May 26.

Department of Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, the Netherlands; Department of Applied Stem Cell Technologies, University of Twente, 7500 Enschede, the Netherlands. Electronic address:

Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284308PMC

A Multiplexed Barcodelet Single-Cell RNA-Seq Approach Elucidates Combinatorial Signaling Pathways that Drive ESC Differentiation.

Cell Stem Cell 2020 Jun 26;26(6):938-950.e6. Epub 2020 May 26.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Hubrecht Institute, 3584 CT Utrecht, the Netherlands. Electronic address:

Empirical optimization of stem cell differentiation protocols is time consuming, is laborintensive, and typically does not comprehensively interrogate all relevant signaling pathways. Here we describe barcodelet single-cell RNA sequencing (barRNA-seq), which enables systematic exploration of cellular perturbations by tagging individual cells with RNA "barcodelets" to identify them on the basis of the treatments they receive. We apply barRNA-seq to simultaneously manipulate up to seven developmental pathways and study effects on embryonic stem cell (ESC) germ layer specification and mesodermal specification, uncovering combinatorial effects of signaling pathway activation on gene expression. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.020DOI Listing

A Non-Coding Disease Modifier of Pancreatic Agenesis Identified by Genetic Correction in a Patient-Derived iPSC Line.

Cell Stem Cell 2020 Jul 21;27(1):137-146.e6. Epub 2020 May 21.

Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:

GATA6 is a critical regulator of pancreatic development, with heterozygous mutations in this transcription factor being the most common cause of pancreatic agenesis. To study the variability in disease phenotype among individuals harboring these mutations, a patient-induced pluripotent stem cell model was used. Interestingly, GATA6 protein expression remained depressed in pancreatic progenitor cells even after correction of the coding mutation. Read More

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http://dx.doi.org/10.1016/j.stem.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335348PMC

Disrupting Mitochondrial Copper Distribution Inhibits Leukemic Stem Cell Self-Renewal.

Cell Stem Cell 2020 Jun 15;26(6):926-937.e10. Epub 2020 May 15.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address:

Leukemic stem cells (LSCs) rely on oxidative metabolism and are differentially sensitive to targeting mitochondrial pathways, which spares normal hematopoietic cells. A subset of mitochondrial proteins is folded in the intermembrane space via the mitochondrial intermembrane assembly (MIA) pathway. We found increased mRNA expression of MIA pathway substrates in acute myeloid leukemia (AML) stem cells. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.010DOI Listing

Integrin-Linked Kinase Mediates Therapeutic Resistance of Quiescent CML Stem Cells to Tyrosine Kinase Inhibitors.

Cell Stem Cell 2020 Jul 14;27(1):110-124.e9. Epub 2020 May 14.

Terry Fox Laboratory, BC Cancer, Vancouver, BC V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Patients with chronic myeloid leukemia (CML) often require lifelong therapy with ABL1 tyrosine kinase inhibitors (TKIs) due to a persisting TKI-resistant population of leukemic stem cells (LSCs). From transcriptome profiling, we show integrin-linked kinase (ILK), a key constituent of focal adhesions, is highly expressed in TKI-nonresponsive patient cells and their LSCs. Genetic and pharmacological inhibition of ILK impaired the survival of nonresponder patient cells, sensitizing them to TKIs, even in the presence of protective niche cells. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.005DOI Listing

Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis.

Cell Stem Cell 2020 Jul 14;27(1):147-157.e7. Epub 2020 May 14.

Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA 02215, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Although susceptibility to cardiovascular disease (CVD) is different for every patient, why some patients with type 2 diabetes mellitus (T2DM) develop CVD while others are protected has not yet been clarified. Using T2DM-patient-derived human induced pluripotent stem cells (hiPSCs), we found that in patients protected from CVD, there was significantly elevated expression of an esterase, arylacetamide deacetylase (AADAC), in vascular smooth muscle cells (VSMCs). We overexpressed this esterase in human primary VSMCs and VSMCs differentiated from hiPSCs and observed that the number of lipid droplets was significantly diminished. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.018DOI Listing

Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis.

Cell Stem Cell 2020 Jul 12;27(1):81-97.e8. Epub 2020 May 12.

The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China. Electronic address:

N-methyladenosine (mA) is a commonly present modification of mammalian mRNAs and plays key roles in various cellular processes. mA modifiers catalyze this reversible modification. However, the underlying mechanisms by which these mA modifiers are regulated remain elusive. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.001DOI Listing

RNA Demethylase ALKBH5 Selectively Promotes Tumorigenesis and Cancer Stem Cell Self-Renewal in Acute Myeloid Leukemia.

Cell Stem Cell 2020 Jul 12;27(1):64-80.e9. Epub 2020 May 12.

Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. Electronic address:

N-methyladenosine (mA), the most abundant internal modification in mRNA, has been implicated in tumorigenesis. As an mA demethylase, ALKBH5 has been shown to promote the development of breast cancer and brain tumors. However, in acute myeloid leukemia (AML), ALKBH5 was reported to be frequently deleted, implying a tumor-suppressor role. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335338PMC

A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells.

Cell Stem Cell 2020 Jul 11;27(1):158-176.e10. Epub 2020 May 11.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address:

The developmental trajectory of human skeletal myogenesis and the transition between progenitor and stem cell states are unclear. We used single-cell RNA sequencing to profile human skeletal muscle tissues from embryonic, fetal, and postnatal stages. In silico, we identified myogenic as well as other cell types and constructed a "roadmap" of human skeletal muscle ontogeny across development. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.017DOI Listing

Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer.

Cell Stem Cell 2020 Jun 11;26(6):845-861.e12. Epub 2020 May 11.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028 Barcelona, Spain; ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 08028 Barcelona, Spain. Electronic address:

Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.012DOI Listing

ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress.

Cell Stem Cell 2020 May 11. Epub 2020 May 11.

Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela (USC)-Health Research Institute (IDIS), Santiago de Compostela 15782, Spain; Department of Physiology, USC, Santiago de Compostela 15782, Spain. Electronic address:

RNA editing of adenosine to inosine (A to I) is catalyzed by ADAR1 and dramatically alters the cellular transcriptome, although its functional roles in somatic cell reprogramming are largely unexplored. Here, we show that loss of ADAR1-mediated A-to-I editing disrupts mesenchymal-to-epithelial transition (MET) during induced pluripotent stem cell (iPSC) reprogramming and impedes acquisition of induced pluripotency. Using chemical and genetic approaches, we show that absence of ADAR1-dependent RNA editing induces aberrant innate immune responses through the double-stranded RNA (dsRNA) sensor MDA5, unleashing endoplasmic reticulum (ER) stress and hindering epithelial fate acquisition. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.016DOI Listing

FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits.

Cell Stem Cell 2020 Jul 7;27(1):98-109.e11. Epub 2020 May 7.

Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich, Zurich 8057, Switzerland. Electronic address:

Altered neural stem/progenitor cell (NSPC) activity and neurodevelopmental defects are linked to intellectual disability. However, it remains unclear whether altered metabolism, a key regulator of NSPC activity, disrupts human neurogenesis and potentially contributes to cognitive defects. We investigated links between lipid metabolism and cognitive function in mice and human embryonic stem cells (hESCs) expressing mutant fatty acid synthase (FASN; R1819W), a metabolic regulator of rodent NSPC activity recently identified in humans with intellectual disability. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.002DOI Listing

Hematopoietic Stem and Progenitor Cells Exhibit Stage-Specific Translational Programs via mTOR- and CDK1-Dependent Mechanisms.

Cell Stem Cell 2020 May;26(5):755-765.e7

Department of Pathology, NYU School of Medicine, New York, NY 10016, USA. Electronic address:

Hematopoietic stem cells (HSCs) require highly regulated rates of protein synthesis, but it is unclear if they or lineage-committed progenitors preferentially recruit transcripts to translating ribosomes. We utilized polysome profiling, RNA sequencing, and whole-proteomic approaches to examine the translatome in LSK (LinSca-1c-Kit) and myeloid progenitor (MP; LinSca-1c-Kit) cells. Our studies show that LSKs exhibit low global translation but high translational efficiencies (TEs) of mRNAs required for HSC maintenance. Read More

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http://dx.doi.org/10.1016/j.stem.2019.12.006DOI Listing

Tools and Concepts for Interrogating and Defining Cellular Identity.

Cell Stem Cell 2020 May;26(5):632-656

Department of Orofacial Sciences, University of California, San Francisco, San Francisco, CA, USA; Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Defining the mechanisms that generate specialized cell types and coordinate their functions is critical for understanding organ development and renewal. New tools and discoveries are challenging and refining our definitions of a cell type. A rapidly growing toolkit for single-cell analyses has expanded the number of markers that can be assigned to a cell simultaneously, revealing heterogeneity within cell types that were previously regarded as homogeneous populations. Read More

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http://dx.doi.org/10.1016/j.stem.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250495PMC

High-Fidelity Modeling of Human Microglia with Pluripotent Stem Cells.

Cell Stem Cell 2020 May;26(5):629-631

Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.

Gosselin et al. (2017) reported that a tissue-environment-dependent transcriptional network specifies human microglia identity and that in vitro environments drastically alter the human microglia transcriptome. Recent 3-dimensional culture and human-mouse chimeric brain modeling systems developed using human pluripotent stem cells help us understand the complex properties of human microglia. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262396PMC

The Advocate's Adventure.

Authors:
Don C Reed

Cell Stem Cell 2020 May;26(5):620-626

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http://dx.doi.org/10.1016/j.stem.2020.04.006DOI Listing

Problems and Pitfalls of Identifying Remyelination in Multiple Sclerosis.

Cell Stem Cell 2020 May;26(5):617-619

Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address:

Regenerative medicines that promote remyelination in multiple sclerosis (MS) are making the transition from laboratory to clinical trials. While animal models provide the experimental flexibility to analyze mechanisms of remyelination, here we discuss the challenges in understanding where and how remyelination occurs in MS. Read More

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http://dx.doi.org/10.1016/j.stem.2020.03.017DOI Listing

APA Makes a Short Cut for Ramping up HSC Metabolism.

Authors:
Shuai Jiang

Cell Stem Cell 2020 May;26(5):615-616

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Electronic address:

The physiological role of alternative polyadenylation (APA) in controlling hematopoietic stem cell (HSC) behavior in vivo, and the mechanistic implications of this association, remain elusive. Now in Cell Stem Cell, Sommerkamp et al. (2020) provide evidence that APA regulates HSC self-renewal and multi-potency by affecting stem cell activation and glutaminolysis. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.007DOI Listing

Tales from the Cryptkeeper: New Roles for Lats1/2 in Wnt-driven Homeostasis.

Cell Stem Cell 2020 May;26(5):612-614

Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

In this issue of Cell Stem Cell, Li et al. (2020) reveal pivotal roles for Lats1/2 in adult, Wnt-mediated intestinal homeostasis through TEAD-dependent and -independent transcription. Loss of Lats1/2 mobilizes a previously unrecognized YAP/TAZ-Groucho/TLE interaction to suppress Wnt/TCF-mediated transcription, thereby resulting in intestinal stem cell depletion and Wnt-uncoupled progenitor expansion. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.011DOI Listing

Inflammation's Epigenetic Footprint in Hematopoietic Stem Cells.

Cell Stem Cell 2020 May;26(5):611-612

Division Inflammatory Stress in Stem Cells, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), 69120 Heidelberg, Germany; DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. Electronic address:

Immune memory was thought to be unique to cells of the adaptive immune system. In this issue of Cell Stem Cell, de Laval et al. (2020) describe persistent epigenetic modifications in hematopoietic stem cells following an inflammatory insult with LPS as a mechanism by which immune memory may be established. Read More

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http://dx.doi.org/10.1016/j.stem.2020.04.015DOI Listing