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Genome-wide maps of chromatin state in cultured male germline stem cells with retinoic acid treatment [scATAC-seq]

ABSTRACT: Genome-wide maps of chromatin state in cultured male germline stem cells with retinoic acid treatment [scATAC-seq]

PROVIDER: PRJNA704903 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13783625_1.fastq.gz	Fastqsanger.gz
	SRR13783625_2.fastq.gz	Fastqsanger.gz

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Genome-wide maps of chromatin state in cultured male germline stem cells with retinoic acid treatment [scATAC-seq]

Project description:We report the application of single-cell ATAC-seq to reconstruct the epigenetic program and differentiation trajectory associated with the retinoic acid (RA)-induced differentiation in cultured male germline stem cells (GSCs). We also identified key transcription factors and regulatory elements regulated by RA.

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Genome-wide maps of chromatin state in cultured male germline stem cells [scATAC-seq]

Project description:Genome-wide maps of chromatin state in cultured male germline stem cells [scATAC-seq]

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Genome-wide maps of chromatin state in cultured male germline stem cells [scATAC-seq]

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.

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scATAC-Seq reveals heterogeneity associated with spermatogonial differentiation in cultured male germline stem cells.

Project description:Spermatogonial stem cells are the most primitive spermatogonia in testis, which can self-renew to maintain the stem cell pool or differentiate to give rise to germ cells including haploid spermatids. All-trans-retinoic acid (RA), a bioactive metabolite of vitamin A, plays a fundamental role in initiating spermatogonial differentiation. In this study, single-cell ATAC-seq (scATAC-seq) was used to obtain genome-wide chromatin maps of cultured germline stem cells (GSCs) that were in control and RA-induced differentiation states. We showed that different subsets of GSCs can be distinguished based on chromatin accessibility of self-renewal and differentiation signature genes. Importantly, both progenitors and a subset of stem cells are able to respond to RA and give rise to differentiating cell subsets with distinct chromatin accessibility profiles. In this study, we identified regulatory regions that undergo chromatin remodeling and are associated with the retinoic signaling pathway. Moreover, we reconstructed the differentiation trajectory and identified novel transcription factor candidates enriched in different spermatogonia subsets. Collectively, our work provides a valuable resource for understanding the heterogeneity associated with differentiation and RA response in GSCs.

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The SMARCA5–DMRT1 Pioneer Complex Establishes Epigenetic Priming to Direct Male Germline Development [RNA-Seq]

Project description:Establishing cell type–specific chromatin landscapes is essential for cellular identity, yet how these landscapes are generated and maintained remains poorly understood. Here, we demonstrate that the chromatin remodeler SMARCA5 facilitates epigenetic priming required for retinoic acid–induced differentiation in the male germline. Germ cell–specific deletion of Smarca5 results in a complete loss of differentiating spermatogonia, phenocopying vitamin A–deficient mice lacking retinoic acid signaling. During the perinatal transition from prospermatogonia to undifferentiated spermatogonia, SMARCA5 is recruited to DMRT1-binding sites located at distal putative enhancers and promoters of germline genes. The SMARCA5–DMRT1 pioneer complex establishes chromatin accessibility at these loci, generating poised enhancers and promoters that serve as retinoic acid receptor (RAR)–binding sites. Thus, SMARCA5 licenses transcriptional responses to retinoic acid that enable spermatogenic differentiation. Our findings uncover a critical epigenetic priming mechanism that links pioneer factor activity to external signal responsiveness in the germline.

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