705 results match your criteria tracing single-cell

Progress towards a cellularly resolved mouse mesoconnectome is empowered by data fusion and new neuroanatomy techniques.

Neurosci Biobehav Rev 2021 Jun 10. Epub 2021 Jun 10.

Neuroinformatics department, Donders Centre for Neuroscience, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.

Over the past decade there has been a rapid improvement in techniques for obtaining large-scale cellular level data related to the mouse brain connectome. However, a detailed mapping of cell-type-specific projection patterns is lacking, which would, for instance, allow us to study the role of circuit motifs in cognitive processes. In this work, we review advanced neuroanatomical and data fusion techniques within the context of a proposed Multimodal Connectomic Integration Framework for augmenting the cellularly resolved mouse mesoconnectome. Read More

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Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states.

Cancer Cell 2021 May 28. Epub 2021 May 28.

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we recover ∼380,000 CRISPR target sites and reconstruct dissemination of ∼28,000 single cells across multiple metastatic sites. Read More

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Tracing the origin of hair follicle stem cells.

Nature 2021 Jun 9. Epub 2021 Jun 9.

Laboratory for Tissue Microenvironment, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events. Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging and single-cell transcriptomics to capture a dynamic lineage progression and transcriptome changes in the entire epithelium of the mouse hair follicle as it develops. Read More

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Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization.

Cell Stem Cell 2021 Jun 2. Epub 2021 Jun 2.

Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Stem cells support lifelong maintenance of adult organs, but their specific roles during injury are poorly understood. Here we demonstrate that Lgr6 marks a regionally restricted population of epidermal stem cells that interact with nerves and specialize in wound re-epithelialization. Diphtheria toxin-mediated ablation of Lgr6 stem cells delays wound healing, and skin denervation phenocopies this effect. Read More

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Nkx2-2 expressing taste cells in endoderm-derived taste papillae are committed to the type III lineage.

Dev Biol 2021 Jun 5;477:232-240. Epub 2021 Jun 5.

Monell Chemical Senses Center, Philadelphia, PA, USA.

In mammals, multiple cell-signaling pathways and transcription factors regulate development of the embryonic taste system and turnover of taste cells in the adult stage. Using single-cell RNA-Seq of mouse taste cells, we found that the homeobox-containing transcription factor Nkx2-2, a target of the Sonic Hedgehog pathway and a key regulator of the development and regeneration of multiple cell types in the body, is highly expressed in type III taste cells but not in type II or taste stem cells. Using in situ hybridization and immunostaining, we confirmed that Nkx2-2 is expressed specifically in type III taste cells in the endoderm-derived circumvallate and foliate taste papillae but not in the ectoderm-derived fungiform papillae. Read More

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Single-cell transcriptomic analysis reveals a hepatic stellate cell-activation roadmap and myofibroblast origin during liver fibrosis.

Hepatology 2021 Jun 5. Epub 2021 Jun 5.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

Hepatic stellate cells (HSCs) and portal fibroblasts (PFs) are the major sources of collagen-producing myofibroblasts during liver fibrosis, depending on different etiologies. However, the mechanisms by which their dynamic gene expression directs the transition from the quiescent to the activated state-as well as their contributions to fibrotic myofibroblasts-remain unclear. Here, we analyze the activation of HSCs and PFs in CCL - and bile duct ligation (BDL)-induced fibrosis mouse models, using single-cell RNA-sequencing and lineage tracing. Read More

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Illuminating Neural Circuits in Alzheimer's Disease.

Neurosci Bull 2021 Jun 5. Epub 2021 Jun 5.

Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no cure. Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with AD. Therefore, it is important to understand the structural features and mechanisms underlying the deregulated circuits during AD progression, by which new tools for intervention can be developed. Read More

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Conservation of neural progenitor identity and the emergence of neocortical neuronal diversity.

Semin Cell Dev Biol 2021 May 31. Epub 2021 May 31.

The University of Queensland, Queensland Brain Institute, Brisbane, Queensland 4072, Australia. Electronic address:

One paramount challenge for neuroscientists over the past century has been to identify the embryonic origins of the enormous diversity of cortical neurons found in the adult human neocortex and to unravel the developmental processes governing their emergence. In all mammals, including humans, the radial glia lining the ventricles of the embryonic telencephalon, more recently reclassified as apical radial glia (aRGs), have been identified as the neural progenitors giving rise to all excitatory neurons and inhibitory interneurons of the six-layered cortex. In this review, we explore the fundamental molecular and cellular mechanisms that regulate aRG function and the generation of neuronal diversity in the dorsal telencephalon. Read More

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Regulation and Role of Transcription Factors in Osteogenesis.

Int J Mol Sci 2021 May 21;22(11). Epub 2021 May 21.

School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.

Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. Read More

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In Vivo Tracking of Hematopoietic Stem and Progenitor Cell Ontogeny by Cellular Barcoding.

Methods Mol Biol 2021 ;2308:281-300

Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, Paris, France.

Cellular barcoding is a powerful technique that allows for high-throughput mapping of the fate of single cells, notably hematopoietic stem and progenitor cells (HSPCs) after transplantation. Unique artificial DNA fragments, termed barcodes, are stably inserted into HSPCs using lentiviral transduction, making sure that each individual cell receives a single unique barcode. Barcoded HSPCs are transplanted into sublethally irradiated mice where they reconstitute the hematopoietic system through proliferation and differentiation. Read More

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January 2021

Flow Cytometry-Based Analysis of the Mouse Bone Marrow Stromal and Perivascular Compartment.

Methods Mol Biol 2021 ;2308:83-94

University of Michigan School of Dentistry, Ann Arbor, MI, USA.

Bone marrow stromal cells (BMSCs) account for an extremely small percentage of total bone marrow cells; therefore, it is technically challenging to harvest a good quantity of BMSCs with good viability using fluorescence-activated cell sorting (FACS). Here, we describe the methods to effectively isolate BMSCs for flow cytometry analyses and subsequent FACS. Use of transgenic reporter lines facilitates FACS-based isolation of BMSCs, aiding to uncover fundamental characteristics of these diverse cell populations. Read More

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January 2021

Defining the Emerging Blood System During Development at Single-Cell Resolution.

Front Cell Dev Biol 2021 12;9:660350. Epub 2021 May 12.

Division of Molecular Hematology, Lund Stem Cell Center, Lund University, Lund, Sweden.

Developmental hematopoiesis differs from adult and is far less described. In the developing embryo, waves of lineage-restricted blood precede the ultimate emergence of definitive hematopoietic stem cells (dHSCs) capable of maintaining hematopoiesis throughout life. During the last two decades, the advent of single-cell genomics has provided tools to circumvent previously impeding characteristics of embryonic hematopoiesis, such as cell heterogeneity and rare cell states, allowing for definition of lineage trajectories, cellular hierarchies, and cell-type specification. Read More

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Understanding the Adult Mammalian Heart at Single-Cell RNA-Seq Resolution.

Front Cell Dev Biol 2021 12;9:645276. Epub 2021 May 12.

Department of Animal Biology, Faculty of Sciences, Instituto Malagueño de Biomedicina, University of Málaga, Málaga, Spain.

During the last decade, extensive efforts have been made to comprehend cardiac cell genetic and functional diversity. Such knowledge allows for the definition of the cardiac cellular interactome as a reasonable strategy to increase our understanding of the normal and pathologic heart. Previous experimental approaches including cell lineage tracing, flow cytometry, and bulk RNA-Seq have often tackled the analysis of cardiac cell diversity as based on the assumption that cell types can be identified by the expression of a single gene. Read More

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Generative modeling of single-cell time series with PRESCIENT enables prediction of cell trajectories with interventions.

Nat Commun 2021 05 28;12(1):3222. Epub 2021 May 28.

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.

Existing computational methods that use single-cell RNA-sequencing (scRNA-seq) for cell fate prediction do not model how cells evolve stochastically and in physical time, nor can they predict how differentiation trajectories are altered by proposed interventions. We introduce PRESCIENT (Potential eneRgy undErlying Single Cell gradIENTs), a generative modeling framework that learns an underlying differentiation landscape from time-series scRNA-seq data. We validate PRESCIENT on an experimental lineage tracing dataset, where we show that PRESCIENT is able to predict the fate biases of progenitor cells in hematopoiesis when accounting for cell proliferation, improving upon the best-performing existing method. Read More

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The multiple facets of Cajal-Retzius neurons.

Development 2021 Jun 28;148(11). Epub 2021 May 28.

Institute of Physiology, University Medical Center of the Johannes Gutenberg University Mainz, D-55128 Mainz, Germany.

Cajal-Retzius neurons (CRs) are among the first-born neurons in the developing cortex of reptiles, birds and mammals, including humans. The peculiarity of CRs lies in the fact they are initially embedded into the immature neuronal network before being almost completely eliminated by cell death at the end of cortical development. CRs are best known for controlling the migration of glutamatergic neurons and the formation of cortical layers through the secretion of the glycoprotein reelin. Read More

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A finger on the pulse of regeneration: insights into the cellular mechanisms of adult digit tip regeneration.

Curr Opin Genet Dev 2021 May 24;70:1-6. Epub 2021 May 24.

Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4 Canada; Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z4 Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, V6T 1Z4 Canada. Electronic address:

In mammals, multi-tissue regeneration is largely restricted to the distal portion of the digit tip and involves the formation of a blastema, a transient, proliferating cell mass that reforms the diverse tissues of the digit. Historically little was known about the mammalian blastema but with recent advances in single cell transcriptomic approaches and genetic lineage tracing, a more precise understanding of this critical structure has begun to emerge. In this review we summarise the cellular mechanisms underlying adult mammalian digit tip regeneration. Read More

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One-Cell Metabolic Phenotyping and Sequencing of Soil Microbiome by Raman-Activated Gravity-Driven Encapsulation (RAGE).

mSystems 2021 May 27:e0018121. Epub 2021 May 27.

Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Institute of Energy Research, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.

Soil harbors arguably the most metabolically and genetically heterogeneous microbiomes on Earth, yet establishing the link between metabolic functions and genome at the precisely one-cell level has been difficult. Here, for mock microbial communities and then for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) platform, which identifies, sorts, and sequences precisely one bacterial cell via its anabolic (incorporating D from heavy water) and physiological (carotenoid-containing) functions. We showed that (i) metabolically active cells from numerically rare soil taxa, such as spp. Read More

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Fate and State of Vascular Smooth Muscle Cells in Atherosclerosis.

Circulation 2021 May 24;143(21):2110-2116. Epub 2021 May 24.

Center for Developmental Biology and Regenerative Medicine, Department of Pediatrics, University of Washington, Seattle Children's Research Institute (M.W.M.).

Vascular smooth muscle cells (VSMCs) have long been associated with phenotypic modulation/plasticity or dedifferentiation. Innovative technologies in cell lineage tracing, single-cell RNA sequencing, and human genomics have been integrated to gain unprecedented insights into the molecular reprogramming of VSMCs to other cell phenotypes in experimental and clinical atherosclerosis. The current thinking is that an apparently small subset of contractile VSMCs undergoes a fate switch to transitional, multipotential cells that can adopt plaque-destabilizing (inflammation, ossification) or plaque-stabilizing (collagen matrix deposition) cell states. Read More

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QPLOT Neurons-Converging on a Thermoregulatory Preoptic Neuronal Population.

Front Neurosci 2021 4;15:665762. Epub 2021 May 4.

The Visual Systems Group, Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

The preoptic area of the hypothalamus is a homeostatic control center. The heterogeneous neurons in this nucleus function to regulate the sleep/wake cycle, reproduction, thirst and hydration, as well as thermogenesis and other metabolic responses. Several recent studies have analyzed preoptic neuronal populations and demonstrated neuronal subtype-specific roles in suppression of thermogenesis. Read More

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Temporal single-cell regeneration studies: the greatest thing since sliced pancreas?

Trends Endocrinol Metab 2021 Jul 15;32(7):433-443. Epub 2021 May 15.

Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address:

The application of single-cell analytic techniques to the study of stem/progenitor cell niches supports the emerging view that pancreatic cell lineages are in a state of flux between differentiation stages. For all their value, however, such analyses merely offer a snapshot of the cellular palette of the tissue at any given time point. Conclusions about potential developmental/regeneration paths are solely based on bioinformatics inferences. Read More

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Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak.

PLoS Biol 2021 May 17;19(5):e3001200. Epub 2021 May 17.

The Francis Crick Institute, London, United Kingdom.

The heart develops from 2 sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay combined with genetic lineage tracing and live imaging, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. Read More

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Current progress and potential opportunities to infer single-cell developmental trajectory and cell fate.

Curr Opin Syst Biol 2021 Jun 26;26:1-11. Epub 2021 Mar 26.

Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital Research Institute, Charlestown, USA.

Rapid technological advances in transcriptomics and lineage tracing technologies provide new opportunities to understand organismal development at the single-cell level. Building on these advances, various computational methods have been proposed to infer developmental trajectories and to predict cell fate. These methods have unveiled previously uncharacterized transitional cell types and differentiation processes. Read More

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Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease.

Front Cell Neurosci 2021 29;15:673132. Epub 2021 Apr 29.

Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, United Kingdom.

Oligodendrocyte progenitor cells (OPCs), also referred to as NG2-glia, are the most proliferative cell type in the adult central nervous system. While the primary role of OPCs is to serve as progenitors for oligodendrocytes, in recent years, it has become increasingly clear that OPCs fulfil a number of other functions. Indeed, independent of their role as stem cells, it is evident that OPCs can regulate the metabolic environment, directly interact with and modulate neuronal function, maintain the blood brain barrier (BBB) and regulate inflammation. Read More

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The inflammatory speech of fibroblasts.

Immunol Rev 2021 May 13. Epub 2021 May 13.

Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.

Activation of fibroblasts is a key event during normal tissue repair after injury and the dysregulated repair processes that result in organ fibrosis. To most researchers, fibroblasts are rather unremarkable spindle-shaped cells embedded in the fibrous collagen matrix of connective tissues and/or deemed useful to perform mechanistic studies with adherent cells in culture. For more than a century, fibroblasts escaped thorough classification due to the lack of specific markers and were treated as the leftovers after all other cells have been identified from a tissue sample. Read More

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Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing.

Cell Stem Cell 2021 May 8. Epub 2021 May 8.

Department of Genetics & Developmental Biology, The Rappaport Faculty of Medicine & Research Institute, Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address:

The accessibility and transparency of the cornea permit robust stem cell labeling and in vivo cell fate mapping. Limbal epithelial stem cells (LSCs) that renew the cornea are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. Here, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. Read More

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Lineage tracing of human development through somatic mutations.

Nature 2021 May 12. Epub 2021 May 12.

Wellcome Trust Sanger Institute, Hinxton, UK.

The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations. Here we reconstruct a phylogenetic tree of blood development using whole-genome sequencing of 511 single-cell-derived haematopoietic colonies from healthy human fetuses at 8 and 18 weeks after conception, coupled with deep targeted sequencing of tissues of known embryonic origin. We found that, in healthy fetuses, individual haematopoietic progenitors acquire tens of somatic mutations by 18 weeks after conception. Read More

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A stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration.

Nat Commun 2021 05 12;12(1):2761. Epub 2021 May 12.

Aix-Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Team, Marseille, France.

At numerous locations of the body, transition zones are localized at the crossroad between two types of epithelium and are frequently associated with neoplasia involving both type of tissues. These transition zones contain cells expressing markers of adult stem cells that can be the target of early transformation. The mere fact that transition zone cells can merge different architecture with separate functions implies for a unique plasticity that these cells must display in steady state. Read More

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Isotopic tracing reveals single-cell assimilation of a macroalgal polysaccharide by a few marine Flavobacteria and Gammaproteobacteria.

ISME J 2021 May 5. Epub 2021 May 5.

Institut Curie, Université Paris-Saclay, Paris, France.

Algal polysaccharides constitute a diverse and abundant reservoir of organic matter for marine heterotrophic bacteria, central to the oceanic carbon cycle. We investigated the uptake of alginate, a major brown macroalgal polysaccharide, by microbial communities from kelp-dominated coastal habitats. Congruent with cell growth and rapid substrate utilization, alginate amendments induced a decrease in bacterial diversity and a marked compositional shift towards copiotrophic bacteria. Read More

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The embryonic ontogeny of the gonadal somatic cells in mice and monkeys.

Cell Rep 2021 May;35(5):109075

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto 606-8501, Japan; Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan. Electronic address:

In the early fetal stage, the gonads are bipotent and only later become the ovary or testis, depending on the genetic sex. Despite many studies examining how sex determination occurs from biopotential gonads, the spatial and temporal organization of bipotential gonads and their progenitors is poorly understood. Here, using lineage tracing in mice, we find that the gonads originate from a T primitive streak through WT1 posterior intermediate mesoderm and appear to share origins anteriorly with the adrenal glands and posteriorly with the metanephric mesenchyme. Read More

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The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration.

Sci China Life Sci 2021 Apr 30. Epub 2021 Apr 30.

National Institute of Biological Sciences, Beijing, 102206, China.

The adult lung, a workhorse for gas exchange, is continually subjected to a barrage of assaults from the inhaled particles and pathogens. Hence, homeostatic maintenance is of paramount importance. Epithelial stem cells interact with their particular niche in the adult lung to orchestrate both natural tissue rejuvenation and robust post-injury regeneration. Read More

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