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Regulation of human germline commitment by DMRT1 [scRNA-Seq]

ABSTRACT: Regulation of human germline commitment by DMRT1 [scRNA-Seq]

PROVIDER: PRJNA924744 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23098051.fastq.gz	Fastqsanger.gz
	SRR23098052.fastq.gz	Fastqsanger.gz
	SRR23098053.fastq.gz	Fastqsanger.gz
	SRR23098054.fastq.gz	Fastqsanger.gz
	SRR23098055.fastq.gz	Fastqsanger.gz

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Regulation of human germline commitment by DMRT1

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Project description:Nascent human primordial germ cell-like cells (PGCLCs) can be specified with BMP2 or BMP4 together with SCF and EGF from germline competent embryonic stem cells which are maintained in the presence of inhibitors for GSK3, MEK, p38 and JNK together with FGF2, TGFβ and LIF (4i ESC). Here we discovered that Activin A and retinoic acid treatment after PGC specification induced genes expressed in migrating and gonadal PGCs in vivo, including DMRT1 and CDH5. Ectopic expression of DMRT1 and SOX17 resulted in repression of pluripotent genes as well as induction of DAZL and a subset of mitotic arrest PGC genes. Our findings provide novel insights on the roles of DMRT1 for the transition from nascent PGCs towards germline determination and molecular mechanisms of early human germline development.

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DMRT1 regulates human germline commitment.

Project description:Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.

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