527 results match your criteria maturation editing

Osmotic stress-induced somatic embryo maturation of coffee Coffea arabica L., shoot and root apical meristems development and robustness.

Sci Rep 2021 May 6;11(1):9661. Epub 2021 May 6.

Departamento de Ingeniería Genética, Centro de Investigación y Estudios Avanzados del IPN (CINVESTAV), Unidad Irapuato, Km. 9.6 Libramiento Norte Carretera Irapuato-León, CP 36824, Irapuato, Guanajuato, Mexico.

Somatic embryogenesis (SE) is the most important plant biotechnology process for plant regeneration, propagation, genetic transformation and genome editing of coffee, Coffea arabica L. Somatic embryo (SEs) conversion to plantlets is the principal bottleneck for basic and applied use of this process. In this study we focus on the maturation of SEs of C. Read More

View Article and Full-Text PDF

Loss of Increases Germ Cell Apoptosis but Is Still Compatible With Sperm Production in Atlantic Salmon ().

Front Cell Dev Biol 2021 16;9:657192. Epub 2021 Apr 16.

Institute of Marine Research, Research Group Reproduction and Developmental Biology, Bergen, Norway.

Entering meiosis strictly depends on () gene function in mammals. This gene is missing in a number of fish species, including medaka and zebrafish, but is present in the majority of fishes, including Atlantic salmon. Here, we have examined the effects of removing on male fertility in Atlantic salmon. Read More

View Article and Full-Text PDF

Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis .

Front Immunol 2021 25;12:642198. Epub 2021 Mar 25.

Transplantation Research and Immunology Group, John Radcliffe Hospital, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.

Humanized immune system (HIS) mouse models are useful tools for the investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. Read More

View Article and Full-Text PDF

Eltrombopag Improves Erythroid Differentiation in a Human Induced Pluripotent Stem Cell Model of Diamond Blackfan Anemia.

Cells 2021 Mar 26;10(4). Epub 2021 Mar 26.

Cellular and Molecular Therapeutics Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Diamond Blackfan Anemia (DBA) is a congenital macrocytic anemia associated with ribosomal protein haploinsufficiency. Ribosomal dysfunction delays globin synthesis, resulting in excess toxic free heme in erythroid progenitors, early differentiation arrest, and pure red cell aplasia. In this study, DBA induced pluripotent stem cell (iPSC) lines were generated from blood mononuclear cells of DBA patients with inactivating mutations in RPS19 and subjected to hematopoietic differentiation to model disease phenotypes. Read More

View Article and Full-Text PDF

Introduction of glucan synthase into the cytosol in wheat endosperm causes massive maltose accumulation and represses starch synthesis.

Plant J 2021 Mar 25. Epub 2021 Mar 25.

John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

We expressed a bacterial glucan synthase (Agrobacterium GlgA) in the cytosol of developing endosperm cells in wheat grains, to discover whether it could generate a glucan from cytosolic ADP-glucose. Transgenic lines had high glucan synthase activity during grain filling, but did not accumulate glucan. Instead, grains accumulated very high concentrations of maltose. Read More

View Article and Full-Text PDF

Comparative transcriptomic analysis of the different developmental stages of ovary in red swamp crayfish Procambarus clarkii.

BMC Genomics 2021 Mar 21;22(1):199. Epub 2021 Mar 21.

Guangxi Academy of Fishery Sciences/Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Nanning, 530021, China.

Background: The red swamp crayfish Procambarus clarkii is a freshwater species that possesses high adaptability, environmental tolerance, and fecundity. P. clarkii is artificially farmed on a large scale in China. Read More

View Article and Full-Text PDF

ablation with CRISPR/Cas9 enhances cytotoxicity of human placental stem cell-derived NK cells for cancer immunotherapy.

J Immunother Cancer 2021 Mar;9(3)

Celularity Inc, Florham Park, New Jersey, USA

Background: Tumors often develop resistance to surveillance by endogenous immune cells, which include natural killer (NK) cells. Ex vivo activated and/or expanded NK cells demonstrate cytotoxicity against various tumor cells and are promising therapeutics for adoptive cancer immunotherapy. Genetic modification can further enhance NK effector cell activity or activation sensitization. Read More

View Article and Full-Text PDF

Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia.

Am J Hum Genet 2021 04 17;108(4):709-721. Epub 2021 Mar 17.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong, China; Guangdong Engineering and Technology Research Center for Molecular Diagnostics of Human Genetic Diseases, Guangzhou, 510515 Guangdong, China; Guangdong Engineering and Technology Research Center for Genetic Testing, Guangzhou, 510515 Guangdong, China. Electronic address:

The fetal-to-adult hemoglobin switch is regulated in a developmental stage-specific manner and reactivation of fetal hemoglobin (HbF) has therapeutic implications for treatment of β-thalassemia and sickle cell anemia, two major global health problems. Although significant progress has been made in our understanding of the molecular mechanism of the fetal-to-adult hemoglobin switch, the mechanism of epigenetic regulation of HbF silencing remains to be fully defined. Here, we performed whole-genome bisulfite sequencing and RNA sequencing analysis of the bone marrow-derived GYPA erythroid cells from β-thalassemia-affected individuals with widely varying levels of HbF groups (HbF ≥ 95th percentile or HbF ≤ 5th percentile) to screen epigenetic modulators of HbF and phenotypic diversity of β-thalassemia. Read More

View Article and Full-Text PDF

Current Challenges and Solutions to Tissue Engineering of Large-scale Cardiac Constructs.

Curr Cardiol Rep 2021 03 17;23(5):47. Epub 2021 Mar 17.

Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Research Building III, Columbus, OH, 43215, USA.

Purpose Of Review: Large-scale tissue engineering of cardiac constructs is a rapidly advancing field; however, there are several barriers still associated with the creation and clinical application of large-scale engineered cardiac tissues. We provide an overview of the current challenges and recently (within the last 5 years) described promising solutions to overcoming said challenges.

Recent Findings: The five major criteria yet to be met for clinical application of engineered cardiac tissues are successful electrochemical/mechanical cell coupling, efficient maturation of cardiomyocytes, functional vascularization of large tissues, balancing appropriate immune response, and large-scale generation of constructs. Read More

View Article and Full-Text PDF

Mitochondria: emerging therapeutic strategies for oocyte rescue.

Reprod Sci 2021 Mar 12. Epub 2021 Mar 12.

Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, 100044, China.

As the vital organelles for cell energy metabolism, mitochondria are essential for oocyte maturation, fertilization, and embryo development. Abnormalities in quantity, quality, and function of mitochondria are closely related to poor fertility and disorders, such as decreased ovarian reserve (DOR), premature ovarian aging (POA), and ovarian aging, as well as maternal mitochondrial genetic disease caused by mitochondrial DNA (mtDNA) mutations or deletions. Mitochondria have begun to become a therapeutic target for infertility caused by factors such as poor oocyte quality, oocyte aging, and maternal mitochondrial genetic diseases. Read More

View Article and Full-Text PDF

The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis.

Commun Biol 2021 Mar 12;4(1):336. Epub 2021 Mar 12.

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051, Basel, Switzerland.

Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2α catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. Read More

View Article and Full-Text PDF

Assisted Reproductive Techniques and Genetic Manipulation in the Common Marmoset.

ILAR J 2021 Mar 8. Epub 2021 Mar 8.

Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals in Kawasaki, Kanagawa, Japan.

Genetic modification of nonhuman primate (NHP) zygotes is a useful method for the development of NHP models of human diseases. This review summarizes the recent advances in the development of assisted reproductive and genetic manipulation techniques in NHP, providing the basis for the generation of genetically modified NHP disease models. In this study, we review assisted reproductive techniques, including ovarian stimulation, in vitro maturation of oocytes, in vitro fertilization, embryo culture, embryo transfer, and intracytoplasmic sperm injection protocols in marmosets. Read More

View Article and Full-Text PDF

Impaired neurogenesis in the hippocampus of an adult VPS35 mutant mouse model of Parkinson's disease through interaction with APP.

Neurobiol Dis 2021 Jun 24;153:105313. Epub 2021 Feb 24.

Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, 308433, Singapore; Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, 169857, Singapore; Lee Kong Chian School of Medicine, Nanyang Technology University, Novena Campus, 11 Mandalay Road, 308232, Singapore. Electronic address:

Vacuolar protein sorting protein 35 (VPS35) is a core component of the retromer complex involved in regulating protein trafficking and retrieval. Recently, a missense mutation, Asp620Asn (D620N), in VPS35 (PARK17) has been identified as a pathogenic mutation for late-onset autosomal dominant Parkinson's disease (PD). Although PD is characterized by a range of motor symptoms associated with loss of dopaminergic neurons in the substantial nigra, non-motor symptoms such as impaired hippocampal neurogenesis were observed in both PD patients and animal models of PD caused by multiple PD-linked pathogenic genes such as alpha-synuclein and leucine-rich repeat kinase 2 (LRRK2). Read More

View Article and Full-Text PDF

Functioning of PPR Proteins in Organelle RNA Metabolism and Chloroplast Biogenesis.

Front Plant Sci 2021 9;12:627501. Epub 2021 Feb 9.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China.

The pentatricopeptide repeat (PPR) proteins constitute one of the largest nuclear-encoded protein families in higher plants, with over 400 members in most sequenced plant species. The molecular functions of these proteins and their physiological roles during plant growth and development have been widely studied. Generally, there is mounting evidence that PPR proteins are involved in the post-transcriptional regulation of chloroplast and/or mitochondrial genes, including RNA maturation, editing, intron splicing, transcripts' stabilization, and translation initiation. Read More

View Article and Full-Text PDF
February 2021

Long-term maturation of human cortical organoids matches key early postnatal transitions.

Nat Neurosci 2021 03 22;24(3):331-342. Epub 2021 Feb 22.

Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Human stem-cell-derived models provide the promise of accelerating our understanding of brain disorders, but not knowing whether they possess the ability to mature beyond mid- to late-fetal stages potentially limits their utility. We leveraged a directed differentiation protocol to comprehensively assess maturation in vitro. Based on genome-wide analysis of the epigenetic clock and transcriptomics, as well as RNA editing, we observe that three-dimensional human cortical organoids reach postnatal stages between 250 and 300 days, a timeline paralleling in vivo development. Read More

View Article and Full-Text PDF

Network mapping of primary CD34+ cells by Ampliseq based whole transcriptome targeted resequencing identifies unexplored differentiation regulatory relationships.

PLoS One 2021 5;16(2):e0246107. Epub 2021 Feb 5.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland, Australia.

With the exception of a few master transcription factors, regulators of neutrophil maturation are poorly annotated in the intermediate phenotypes between the granulocyte-macrophage progenitor (GMP) and the mature neutrophil phenotype. Additional challenges in identifying gene expression regulators in differentiation pathways relate to challenges wherein starting cell populations are heterogeneous in lineage potential and development, are spread across various states of quiescence, as well as sample quality and input limitations. These factors contribute to data variability make it difficult to draw simple regulatory inferences. Read More

View Article and Full-Text PDF
February 2021

Dissecting ELANE neutropenia pathogenicity by human HSC gene editing.

Cell Stem Cell 2021 May 28;28(5):833-845.e5. Epub 2021 Jan 28.

Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Broad Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Severe congenital neutropenia (SCN) is a life-threatening disorder most often caused by dominant mutations of ELANE that interfere with neutrophil maturation. We conducted a pooled CRISPR screen in human hematopoietic stem and progenitor cells (HSPCs) that correlated ELANE mutations with neutrophil maturation potential. Highly efficient gene editing of early exons elicited nonsense-mediated decay (NMD), overcame neutrophil maturation arrest in HSPCs from ELANE-mutant SCN patients, and produced normal hematopoietic engraftment function. Read More

View Article and Full-Text PDF

BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells.

Mol Ther 2021 May 21;29(5):1918-1932. Epub 2021 Jan 21.

Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China; Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

Transfusion of red blood cells (RBCs) from ABO-matched but genetically unrelated donors is commonly used for treating anemia and acute blood loss. Increasing demand and insufficient supply for donor RBCs, especially those of universal blood types or free of known and unknown pathogens, has called for ex vivo generation of functional RBCs by large-scale cell culture. However, generating physiological numbers of transfusable cultured RBCs (cRBCs) ex vivo remains challenging, due to our inability to either extensively expand primary RBC precursors (erythroblasts) or achieve efficient enucleation once erythroblasts have been expanded and induced to differentiation and maturation. Read More

View Article and Full-Text PDF

BMP4 activates the Wnt---Wnt pathway to promote primordial germ cell formation via altering H3K4me2.

J Cell Sci 2021 Feb 1;134(3). Epub 2021 Feb 1.

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China

The unique developmental characteristics of chicken primordial germ cells (PGCs) enable them to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits their application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the mechanism underlying chicken PGC formation has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of by inducing β-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the promoter and enhancing H3K4me2 methylation in this region. Read More

View Article and Full-Text PDF
February 2021

Recent progress in pancreatic islet cell therapy.

Inflamm Regen 2021 Jan 5;41(1). Epub 2021 Jan 5.

School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan.

Human pluripotent stem cells (PSCs), including human embryonic stem cells and induced pluripotent stem cells, are promising cell sources in regenerating pancreatic islets through in vitro directed differentiation. Recent progress in this research field has made it possible to generate glucose-responsive pancreatic islet cells from PSCs. Single-cell RNA sequencing techniques have been applied to analyze PSC-derived endocrine beta-cells, which are then compared with human islets. Read More

View Article and Full-Text PDF
January 2021

QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function.

Nat Commun 2021 01 4;12(1):89. Epub 2021 Jan 4.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKI) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. Read More

View Article and Full-Text PDF
January 2021

Mitochondrial RNA quality control in trypanosomes.

Wiley Interdiscip Rev RNA 2021 May 16;12(3):e1638. Epub 2020 Dec 16.

Department of Molecular and Cell Biology, Boston University Medical Campus, Boston, Massachusetts, USA.

Unicellular parasites Trypanosoma brucei spp. cause African human and animal trypanosomiasis, a spectrum of diseases that jeopardize public health and afflict the economy in sub-Saharan Africa. These hemoflagellates are distinguished by a single mitochondrion, which contains a kinetoplast nucleoid composed of DNA and histone-like proteins. Read More

View Article and Full-Text PDF

Selection of a novel AAV2/TNFAIP3 vector for local suppression of islet xenograft inflammation.

Xenotransplantation 2020 Dec 14:e12669. Epub 2020 Dec 14.

Immunology Department, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

Background: Neonatal porcine islets (NPIs) can restore glucose control in mice, pigs, and non-human primates, representing a potential abundant alternative islet supply for clinical beta cell replacement therapy. However, NPIs are vulnerable to inflammatory insults that could be overcome with genetic modifications. Here, we demonstrate in a series of proof-of-concept experiments the potential of the cytoplasmic ubiquitin-editing protein A20, encoded by the TNFAIP3 gene, as an NPI cytoprotective gene. Read More

View Article and Full-Text PDF
December 2020

The deubiquitinase STAMBP modulates cytokine secretion through the NLRP3 inflammasome.

Cell Signal 2021 Mar 27;79:109859. Epub 2020 Nov 27.

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is a multimeric, cytoplasmic, protein complex that regulates maturation and secretion of interleukin (IL)-1β, a potent pro-inflammatory cytokine. Critical to host defense against pathogens, IL-1β amplifies early innate immune responses by activating transcription of numerous other cytokines and chemokines. Excessive IL-1β is associated with poor outcomes in inflammatory illnesses, such as sepsis and the acute respiratory distress syndrome (ARDS). Read More

View Article and Full-Text PDF

Axial Skeletal Malformations in Genetically Modified and .

Comp Med 2020 12 17;70(6):532-541. Epub 2020 Nov 17.

Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California;, Email:

Skeletal malformations in captive-bred, adult spp., have not previously been reported. Here we describe 10 sexually mature, genetically modified laboratory frogs (6 and 4 ) with axial skeletal abnormalities. Read More

View Article and Full-Text PDF
December 2020

An Unexpected Split-Merge Pathway in the Assembly of the Symmetric Nonribosomal Peptide Antibiotic Closthioamide.

Angew Chem Int Ed Engl 2021 02 23;60(8):4104-4109. Epub 2020 Dec 23.

Dept. of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745, Jena, Germany.

Closthioamide (CTA) is a symmetric nonribosomal peptide (NRP) comprised of two diaminopropane-linked polythioamidated monomers. CTA is biosynthesized by Ruminiclostridium cellulolyticum via an atypical NRP synthetase (NRPS)-independent biosynthetic pathway. Although the logic for monomer assembly was recently elucidated, the strategy for the biosynthesis and incorporation of the diamine linker remained a mystery. Read More

View Article and Full-Text PDF
February 2021

Codanin-1 mutations engineered in human erythroid cells demonstrate role of CDAN1 in terminal erythroid maturation.

Exp Hematol 2020 11 16;91:32-38.e6. Epub 2020 Oct 16.

Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY. Electronic address:

The generation of a functional erythrocyte from a committed progenitor requires significant changes in gene expression during hemoglobin accumulation, rapid cell division, and nuclear condensation. Congenital dyserythropoietic anemia type I (CDA-I) is an autosomal recessive disease that presents with erythroid hyperplasia in the bone marrow. Erythroblasts in patients with CDA-I are frequently binucleate and have chromatin bridging and defective chromatin condensation. Read More

View Article and Full-Text PDF
November 2020

Stem Cell-Based Disease Modeling and Cell Therapy.

Xiaowen Bai

Cells 2020 09 29;9(10). Epub 2020 Sep 29.

Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Stem cell science is among the fastest moving fields in biology, with many highly promising directions for translatability. To centralize and contextualize some of the latest developments, this Special Issue presents state-of-the-art research of adult stem cells, induced pluripotent stem cells (iPSCs), and embryonic stem cells as well as cancer stem cells. The studies we include describe efficient differentiation protocols of generation of chondrocytes, adipocytes, and neurons, maturation of iPSC-derived cardiomyocytes and neurons, dynamic characterization of iPSC-derived 3D cerebral organoids, CRISPR/Cas9 genome editing, and non-viral minicircle vector-based gene modification of stem cells. Read More

View Article and Full-Text PDF
September 2020

Self-Organizing Human Induced Pluripotent Stem Cell Hepatocyte 3D Organoids Inform the Biology of the Pleiotropic Gene.

Hepatol Commun 2020 Sep 8;4(9):1316-1331. Epub 2020 Jul 8.

Department of Genetics, Perelman School of Medicine University of Pennsylvania Philadelphia PA.

Establishment of a physiologically relevant human hepatocyte-like cell system for translational research has been hampered by the limited availability of cell models that accurately reflect human biology and the pathophysiology of human disease. Here we report a robust, reproducible, and scalable protocol for the generation of hepatic organoids from human induced pluripotent stem cells (hiPSCs) using short exposure to nonengineered matrices. These hepatic organoids follow defined stages of hepatic development and express higher levels of early (hepatocyte nuclear factor 4A [HNF4A], prospero-related homeobox 1 [PROX1]) and mature hepatic and metabolic markers (albumin, asialoglycoprotein receptor 1 [ASGR1], CCAAT/enhancer binding protein α [C/EBPα]) than two-dimensional (2D) hepatocyte-like cells (HLCs) at day 20 of differentiation. Read More

View Article and Full-Text PDF
September 2020

The erythroblastic island niche: modeling in health, stress, and disease.

Exp Hematol 2020 11 7;91:10-21. Epub 2020 Sep 7.

Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, Scotland, UK. Electronic address:

Erythropoiesis is one of the most demanding processes in the body, with more than 2 million red blood cells produced every second. Multiple hereditary and acquired red blood cell disorders arise from this complex system, with existing treatments effective in managing some of these conditions but few offering a long-term cure. Finding new treatments relies on the full understanding of the cellular and molecular interactions associated with the production and maturation of red blood cells, which take place within the erythroblastic island niche. Read More

View Article and Full-Text PDF
November 2020