Genome-wide maps of chromatin state in cultured male germline stem cells with retinoic acid treatment [scATAC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE167531 | GEO | 2022/12/21
REPOSITORIES: GEO
Similar Datasets
Project description:We report the application of single-cell ATAC-seq to reconstruct the epigenetic program and identify key transcription factors and cis-regulatory elements associated with the epithelial and mesenchymal heterogeneity and G9a inhibition in cultured male germline stem cells (GSCs). First, we identified epithelial-like and mesenchymal-like clusters in the sample. Pseudotime trajectory also indicated that GSCs could undergo EMT-like process with unique regulators in different stages. Lastly, we showed that G9a inhibition could suppress the EMT-like process in GSCs.
2023-07-01 | GSE159414 | GEO
Project description:The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. The purpose of this study was to identify eye-specific genes controlled by RA during photoreceptor differentiation in the zebrafish.
2015-08-28 | GSE63873 | GEO
Project description:The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells through degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knock-out, but LSD1 inhibition sensitizes them to physiological doses of RA without altering the stability of PML-RAR, and extends survival of leukemic mice upon RA treatment. Non-enzymatic activities of LSD1 are essential to block differentiation of leukemic cells, while the combination of LSD1 inhibitors (or LSD1 knock-out) with low doses of RA releases a differentiation-associated gene expression program, not strictly dependent on changes in histone H3K4 methylation (known substrate of LSD1). An integrated proteomic/epigenomic/mutational analysis showed that LSD1 inhibitors alter the recruitment of LSD1-containing complexes to chromatin through inhibition of the interaction between LSD1 and GFI1, a relevant transcription factor in hematopoiesis.
2020-05-26 | PXD012954 | Pride
Project description:The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. The purpose of this study was to identify eye-specific genes controlled by RA during photoreceptor differentiation in the zebrafish. 6 samples; 3 replicates of 2 conditions
2015-08-28 | E-GEOD-63873 | biostudies-arrayexpress
Project description:We aimed to investigate the E-box and Max-independent functions of the oncogene Myc in gene regulation and differentiation of leukemic cells. Expression in HL60 leukemic cells of a mutant form of Myc with impaired Max and E-box interaction by replacing the phosphorylation sites of Pak2 kinase to aspartic acid (MycD), resulted in downregulation of 235 genes and, interestingly, upregulation of 586 genes. Eleven percent of the genes upregulated by MycD coincided with those stimulated by a short treatment of retinoic acid (RA) alone. When leukemic cells expressing MycD were stimulated with RA, the overlap with the RA-alone signature increased to 32% (492/1556 genes). Importantly, 320 of these 492 bona-fide direct RA target genes were specifically superactivated in presence of MycD (MycD+RA>RA), and not by MycA (MycD+RA>MycA+RA), further suggesting a synergy between the two pathways. The list of superactivated genes included important regulators of development and differentiation such as GATA6, ICAM1 and HOX genes, whose expression was validated in independent experiments by RT-qPCR. Induced gene expression in HL60 cells was measured after a short-treatment of retinoic acid (100nM, 4 hours). Cells were either wild-type or expressing ER-tagged MycD or MycA. Four biologically independent experiments were performed at each time.
2012-01-05 | E-GEOD-24731 | biostudies-arrayexpress
Project description:Retinoic acid (RA) induces spermatogonial differentiation, but the mechanism by which it operates remains largely unknown. We developed a germ cell culture assay system to study genes involved in spermatogonial differentiation triggered by RA. Stimulated by Retinoic Acid 8 (Stra8), an RA-inducible gene, is indispensable for meiosis initiation, and its deletion results in a complete block of spermatogenesis at the pre-leptotene/zygotene stage due to failure to complete pre-meiotic DNA replication. To interrogate the role of Stra8 in RA mediated differentiation of spermatogonia, we derived germ cell cultures from the neonatal testis of both wild type and Stra8 knock-out mice. We provide the first evidence that Stra8 plays a crucial role in modulating the responsiveness of undifferentiated spermatogonia to RA and facilitates transition to a differentiated state. Stra8-mediated differentiation is achieved through downregulation of a large portfolio of genes and pathways, most notably including genes involved in the spermatogonial stem cell self-renewal process. We also report here for the first time the role of Transcription Elongation Regulator-1 Like (Tcerg1l) as a downstream effector of RA-induced spermatogonial differentiation.
2021-05-05 | GSE173873 | GEO
Project description:Spermatogonial differentiation is a developmental process that is essential for spermatogenesis, but the molecular and cellular changes that germ cells must undergo to transition from undifferentiated spermatogonia to differentiating spermatogonia remain largely undefined. Retinoic acid (RA) is necessary and sufficient for spermatogonial differentiation. Using the postnatal mouse testis, we examine the transcriptome changes that accompany spermatogonial differentiation. Spermatogenesis was synchronized by administration of potent and selective RA synthesis inhibitor; as a result, testes contained only undifferentiated spermatogonia. Then, the inhibitor was discontinued, and mice were given a single dose of exogenous RA to initiate spermatogonial differentiation. We measured transcriptomes in FACS-enriched germ cells either before RA administration, when the cells correspond to Aal spermatogonia (and a minor contribution of spermatogonial stem cells) or at two points after RA administration, when the cells correspond to A1 or A3 differentiating spermatogonia. The results of this study reveal the full transcriptome changes accompanying spermatogonial differentiation in the mouse.
2023-07-03 | GSE213716 | GEO
Project description:Embryonic stem cells (ESC) are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass in their developmental potential. ESCs pluripotency is maintained through a complex interplay of different signaling pathways and a network of transcription factors, which is centered around Oct3/4, Sox2 and Nanog. Although, in general, much is known about this pluripotency self-renewal circuitry, the molecular events that lead ESC to exit from pluripotency and begin differentiation are currently less known. Retinoic acid, an active metabolite of the vitamin A (retinol), plays important and pleiotropic roles in vertebrate embryonic development and ESC differentiation. Here we demonstrate that RA promotes early steps of ESC differentiation, and that ESC increase their capacity to synthesize RA during spontaneous differentiation as embryoid bodies, up-regulating the RA biosynthetic pathway components RDH1, RDH10, ADH3, RALDH2, and CRABP2. Microarray derived from total RNA of mESC not treated or treated with all-trans retinoic acid (ATRA) for 2 hours.
2016-02-10 | E-GEOD-66043 | biostudies-arrayexpress
Project description:Retinoic acid (RA) is an important developmental signaling molecule responsible for the patterning of multiple vertebrate tissues. RA is also a potent teratogen, causing multi-organ birth defects in humans. Endogenous RA levels must therefore be tightly controlled in the developing embryo. In order to understand the RA function and regulation at the genomic level, we used a microarray approach to identify genes that function as negative feedback regulators of retinoic acid signaling. To that end, we treated embryos with different chemicals: DMSO as control, AGN193019 as RA antagonist at high concentration 10uM and low concentration 1uM, as well as 0.33uM RA. Each treatment has four biological replicates. We screened for genes expressed in early somite-stage embryos that respond oppositely to treatment with RA versus RA antagonists, and validated them by whole-mount RNA in situ hybridization.
2009-05-29 | GSE16264 | GEO
Project description:Retinoic acid (RA) signaling plays a major role in controlling several developmental processes in vertebrate embryos. RA repression of caudal Fgf8 has emerged as a crucial mechanism through which RA controls body axis extension, somitogenesis, and spinal cord neurogenesis. The role of RA in Fgf8 repression is supported by mechanistic studies demonstrating direct RA repression through a nearby RA response element that recruits NCOR in an RA-dependent manner. RA is also required for balanced neuromesodermal progenitor differentiation needed for coordinated generation of mesodermal progenitors for somites and neural progenitors for spinal cord. As many pathways are controlled by RA, we performed RNA-seq analysis comparing wild-type embryos with Aldh1a2 mutants that lack the ability to produce RA. This analysis identified a few hundred genes whose expression is significantly altered when RA is absent, thus providing candidate genes for further analysis to discover RA-regulated genes essential for development.
2019-05-22 | GSE131584 | GEO