Genome-wide examination of ETS1 genomic occupation from pluripotent to cardiac hESC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE129986 | GEO | 2019/09/20
REPOSITORIES: GEO
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Project description:Genome-wide examination of ETS1 genomic occupation from pluripotent to cardiac hESC
| PRJNA533339 | ENA
Project description:We analyzed the global transcriptome signature over the time course of the cardiac differentiation from hESC by RNA-seq. We characterized the genome-wide transcriptome profile of 5 distinct stages; undifferentiated hESC (day 0), mesodermal precursor stage (hMP, day 2), cardiac progenitor stage (hCP, day 5), immature cardiomyocyte (hCM14) and hESC-CMS differentiated for 14 additional days (hCM28). While the stem cell signature decreases over the five stages, the signatures associated with heart and smooth muscle development increase, indicating the efficient cardiac differentiation of our protocol.
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Project description:We report the identification of miRNAs and transcripts that are regulated during human cardiac maturation. Examination of hESC-derived cardiomyocytes , human fetal tissue and human adult heart tissue for cardiomyocyte maturation.
2015-05-12 | E-GEOD-62913 | biostudies-arrayexpress
Project description:The first macrophages that seed the developing heart originate from the yolk sac during fetal life. While murine studies reveal important homeostatic and reparative functions in adults, we know little about their roles in the earliest stages of human heart development due to a lack of accessible tissue. Generation of bioengineered human cardiac microtissues from pluripotent stem cells models these first steps in cardiac tissue development, however macrophages have not been included in these studies. To bridge these gaps, we differentiated human embryonic stem cells (hESCs) into primitive LYVE1+ macrophages (hESC-macrophages; akin to yolk sac macrophages) that stably engrafted within cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts to study reciprocal interactions. Engraftment induced a tissue resident macrophage gene program resembling human fetal cardiac macrophages, enriched in efferocytic pathways. Functionally, hESC-macrophages induced production and maturation of cardiomyocyte sarcomeric proteins, and enhanced contractile force, relaxation kinetics, and electrical properties. Mechanistically, the primary effect of hESC-macrophages was during the stressful events surrounding early microtissue formation, where they engaged in phosphatidylserine dependent ingestion of apoptotic cardiomyocyte cargo, which reinforced core resident macrophage identity, reduced microtissue stress and drove hESC-cardiomyocytes to become more similar to human ventricular cardiomyocytes found in early development, both transcriptionally and metabolically. Inhibiting efferocytosis of hESC-cardiomyocytes by hESC-macrophages led to increased cell stress, impaired sarcomeric protein maturation and reduced cardiac microtissue function (contraction and relaxation). Taken together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development, and reveal a major beneficial, yet previously unappreciated role for human primitive macrophages in enhancing cardiac tissue function.
2024-04-03 | PXD050990 | Pride
Project description:Transcriptomic profiling of hESC-dreived cardiomyocyte on Day 0, 2, 5, 9, 14 and 60 hESC-derived cardiomyocyte via Single cell RNA-seq.
2019-09-20 | GSE129987 | GEO
Project description:Natural killer (NK) cells are innate lymphoid cells that play a critical role in the direct immune defense against tumor cells and pathogens, and additionally have important immune regulatory functions by cytokine secretion. Whereas NK cell biology has been extensively studied in mouse models, transcriptional control of human NK cell differentiation is poorly understood. In this study, we generated ETS1-deficient human embryonic stem cell (hESC) clones using the CRISPR/Cas9 technology. In a complementary approach, we generated ETS1 loss-of-function cord blood hematopoietic stem cells (HSCs) by retroviral transduction of the dominant-negative ETS1 p27 isoform. We show that the transcription factor ETS1 is required for human NK cell differentiation. Transcriptome and ChIP analysis reveal that ETS1 directly regulates expression of several NK cell-linked transcription factors. Also, expression of genes involved in cytokine secretion and cytotoxic activity is ETS1-dependent, whereby these effector functions are decreased in residual NK cells developing from ETS1 loss-of-function cord blood hematopoietic stem cells. Our data show that ETS1 is a critical regulator of human NK cell development and function, and provide important insights in the underlying molecular mechanisms.
2020-10-15 | GSE124103 | GEO
Project description:Natural killer (NK) cells are innate lymphoid cells that play a critical role in the direct immune defense against tumor cells and pathogens, and additionally have important immune regulatory functions by cytokine secretion. Whereas NK cell biology has been extensively studied in mouse models, transcriptional control of human NK cell differentiation is poorly understood. In this study, we generated ETS1-deficient human embryonic stem cell (hESC) clones using the CRISPR/Cas9 technology. In a complementary approach, we generated ETS1 loss-of-function cord blood hematopoietic stem cells (HSCs) by retroviral transduction of the dominant-negative ETS1 p27 isoform. We show that the transcription factor ETS1 is required for human NK cell differentiation. Transcriptome and ChIP analysis reveal that ETS1 directly regulates expression of several NK cell-linked transcription factors. Also, expression of genes involved in cytokine secretion and cytotoxic activity is ETS1-dependent, whereby these effector functions are decreased in residual NK cells developing from ETS1 loss-of-function cord blood hematopoietic stem cells. Our data show that ETS1 is a critical regulator of human NK cell development and function, and provide important insights in the underlying molecular mechanisms.
2020-10-15 | GSE105021 | GEO
Project description:The first macrophages that seed the developing heart originate from the yolk sac during fetal life. While murine studies reveal important homeostatic and reparative functions in adults, we know little about their roles in the earliest stages of human heart development due to a lack of accessible tissue. Generation of bioengineered human cardiac microtissues from pluripotent stem cells models these first steps in cardiac tissue development, however macrophages have not been included in these studies. To bridge these gaps, we differentiated human embryonic stem cells (hESCs) into primitive LYVE1+ macrophages (hESC-macrophages; akin to yolk sac macrophages) that stably engrafted within cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts to study reciprocal interactions. Engraftment induced a tissue resident macrophage gene program resembling human fetal cardiac macrophages, enriched in efferocytic pathways. Functionally, hESC-macrophages induced production and maturation of cardiomyocyte sarcomeric proteins, and enhanced contractile force, relaxation kinetics, and electrical properties. Mechanistically, the primary effect of hESC-macrophages was during the stressful events surrounding early microtissue formation, where they engaged in phosphatidylserine dependent ingestion of apoptotic cardiomyocyte cargo, which reinforced core resident macrophage identity, reduced microtissue stress and drove hESC-cardiomyocytes to become more similar to human ventricular cardiomyocytes found in early development, both transcriptionally and metabolically. Inhibiting efferocytosis of hESC-cardiomyocytes by hESC-macrophages led to increased cell stress, impaired sarcomeric protein maturation and reduced cardiac microtissue function (contraction and relaxation). Taken together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development, and reveal a major beneficial, yet previously unappreciated role for human primitive macrophages in enhancing cardiac tissue function.
2024-04-03 | PXD050996 | Pride
Project description:Expression profiling of Rag2-deficient Ets1++ and Rag2-deficient Ets1-- mature NK cells and WT bone marrow progenitors, WT T cells, and WT Pro B cells WT Hematopoietic progenitors, CD4 T cells, Pro B cells, and WT and Ets1-deficient NK cells were FACs sorted. RNA was subsequently extracted, labelled, and hybridized to Affymetrix microarrays. The goal if this experiment was to identify Ets1 dependent genes in NK cells
2012-08-09 | E-GEOD-37301 | biostudies-arrayexpress