Chromatin occupancy of ATF4 at day 1 of cardiomyocytes differentiation [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA777807 | ENA |
REPOSITORIES: ENA
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Project description:Cardiac development involves large-scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here we show that proteotoxic stress visualized by the misfolded protein aggregates appears during early cardiac differentiation of human embryonic stem cells (hESCs) and is resolved by activation of the PERK branch of the unfolded protein response (UPR). PERK depletion increases misfolded protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of hESCs. Mechanistically, we found that PERK safeguards cardiogenesis through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation-induced proteotoxic stress. Our results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK-ATF4-WARS1 axis.
2023-06-30 | GSE188112 | GEO
Project description:We used AAV to overexpress ATF4 in murine cardiomyocytes in vivo and perfomred bioChIP-Seq to profile the chromatin occupancy of the exogenous protein
2022-05-21 | GSE179958 | GEO
Project description:To characterize transcriptome changes uopn ATF4 or DDIT3 in maturing cardiomyocytes
2022-05-21 | GSE179944 | GEO
Project description:RNA-Seq of ATF4 and DDIT3 OE cardiomyocytes
| PRJNA745958 | ENA
Project description:Human embryonic and induced pluripotent stem cells (hESCs/iPSCs) are promising cell sources for cardiac regenerative medicine. To realize hESC/iPSC-based cardiac cell therapy, efficient induction, purification, and transplantation methods for cardiomyocytes should be required. Though marker gene transduction or fluorescent-based purification methods were reported, fast, efficient and scalable purification methods with no genetic modification are essential for clinical purposes but have not been established yet. In this study, we used microarrays to detail the global gene program during cardiac differentiation and to identify cardiac-specific cell surface markers. hiPSCs (201B6) were differentiated toward cardiomyocytes using a modified-directed differentiation protocol (high density culture in RPMI+B27-insulin, sequential administration of Activin A 100ng/mL 1 day, BMP4 10ng/mL+bFGF 10ng/mL 4 days, and Dkk1 100ng/mL 2 days). Beating clusters were first observed at day 8-9 and spread by day 11 after Activin A administration. Cardiac troponin-T (cTnT)-positive cells appeared at day 7-8 after induction and were observed in 30-70% of cells at day 11. qPCR and genome-wide analysis reflected differentiation processes from the undifferentiated state to cardiomyocytes. Rapid downregulation of pluripotent stem cell markers such as NANOG and POU5F1 was observed within 2 days of differentiation. Early and cardiac mesodermal genes (T, MESP1, KDR, ISL1) were expressed during day 2-5, and cardiac genes (NKX2-5, MYH6, MYH7, MYL2, and MYL7) were expressed after day 7. We identified VCAM1 as a cardiac-specific cell surface marker by microarray and flow cytometry. Human induced pluripotent stem cells (iPSCs; 201B6) were differentiated toward cardiomyocytes (RPMI+B27 medium supplemented d0-1 Activin A, d1-5 BMP4+bFGF, d5-7 Dkk1). RNA was extracted from cells at day 0, day 2, day 5, day 7, day 9, and day 11. Cardiomyocytes appeared after day 7 and reached about 50% of total cells at day 11.
2011-12-31 | E-GEOD-28191 | biostudies-arrayexpress
Project description:ChIP-Seq analysis of ATF4 in cardiomyocytes in vivo
| PRJNA745980 | ENA
Project description:Human embryonic stem cell-reporter line hESC-NKX2.5(eGFP/w) were differentiated to cardiomyocytes (CMs) by utilizing the spin embryoid body method. During differentiation the cells were treated with DMSO or retinoic acid (RA) from day 4-7. At day 31, cells were sorted based on GFP prior to RNA isolation. The results of this microarray demonstrate that CMs treated with RA during differentiation exhibit atrial-like gene expression profile, while DMSO-treated cells show ventricular-like gene profile. CMs treated with DMSO or RA during differentiation were sorted for GFP and analyzed for differential gene expression.
2015-01-01 | E-GEOD-61154 | biostudies-arrayexpress
Project description:Human embryonic stem cell-reporter line hESC-NKX2.5(eGFP/w) were differentiated to cardiomyocytes (CMs) by utilizing the spin embryoid body method. During differentiation the cells were treated with DMSO or retinoic acid (RA) from day 4-7. At day 31, cells were sorted based on GFP prior to RNA isolation. The results of this microarray demonstrate that CMs treated with RA during differentiation exhibit atrial-like gene expression profile, while DMSO-treated cells show ventricular-like gene profile.
2015-01-01 | GSE61154 | GEO
Project description:Human embryonic and induced pluripotent stem cells (hESCs/iPSCs) are promising cell sources for cardiac regenerative medicine. To realize hESC/iPSC-based cardiac cell therapy, efficient induction, purification, and transplantation methods for cardiomyocytes should be required. Though marker gene transduction or fluorescent-based purification methods were reported, fast, efficient and scalable purification methods with no genetic modification are essential for clinical purposes but have not been established yet. In this study, we used microarrays to detail the global gene program during cardiac differentiation and to identify cardiac-specific cell surface markers. hiPSCs (201B6) were differentiated toward cardiomyocytes using a modified-directed differentiation protocol (high density culture in RPMI+B27-insulin, sequential administration of Activin A 100ng/mL 1 day, BMP4 10ng/mL+bFGF 10ng/mL 4 days, and Dkk1 100ng/mL 2 days). Beating clusters were first observed at day 8-9 and spread by day 11 after Activin A administration. Cardiac troponin-T (cTnT)-positive cells appeared at day 7-8 after induction and were observed in 30-70% of cells at day 11. qPCR and genome-wide analysis reflected differentiation processes from the undifferentiated state to cardiomyocytes. Rapid downregulation of pluripotent stem cell markers such as NANOG and POU5F1 was observed within 2 days of differentiation. Early and cardiac mesodermal genes (T, MESP1, KDR, ISL1) were expressed during day 2-5, and cardiac genes (NKX2-5, MYH6, MYH7, MYL2, and MYL7) were expressed after day 7. We identified VCAM1 as a cardiac-specific cell surface marker by microarray and flow cytometry.
2011-12-31 | GSE28191 | GEO
Project description:Activating Transcription Factor 4 (ATF4) is a transcription factor induced by the integrated stress response (ISR). This experiment is a genome-wide occupancy profiling of ATF4 in human HAP1 cells. HAP1 is a near-haploid human cell line that was derived from KBM-7 cells isolated from a patient with Chronic Myelogenous Leukemia. We induced ATF4 expression by mimicking amino acid starvation with the drug histidinol. We identified peaks of ATF4 binding using three independent antibodies. Examination of ATF4 binding in HAP1 cells treated with 2 mM histidinol for 24 hours.
2015-08-28 | E-GEOD-69304 | biostudies-arrayexpress