Segregation of the mammalian germline and soma is policed by Otx2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA479763 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast. Induction requires BMP4 signalling to prospective PGCs and the intrinsic action of PGC transcription factors (TFs). However, the molecular mechanisms connecting BMP4 action to induction of PGC TFs that are responsible for segregation of PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Down-regulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro dramatically increases PGCLC differentiation efficiency and prolongs the period of PGC competence. In the absence of Otx2 activity, PGCLC differentiation becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC TF Blimp1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that Otx2 acts repressively upstream of PGC TFs and functions as a roadblock to prevent the untimely entry of pluripotent stem cells into the PGC lineage, thereby ensuring correct spatio-temporal segregation of the germline and soma.
2018-07-06 | GSE116640 | GEO
Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.
2022-01-24 | GSE159653 | GEO
Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.
2022-01-24 | GSE159649 | GEO
Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.
2022-01-24 | GSE159651 | GEO
Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.
2022-01-24 | GSE159650 | GEO
Project description:Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.
2022-01-24 | GSE159652 | GEO
Project description:To define what genes are predominantly or specifically expressed in either soma or germline in C. elegans adults, total RNA was extracted from germline-less glp-4 mutant animals or from dissected gonads, respectively. Total RNA sequencing was peformed in duplicates. Four samples in total.
2015-01-08 | E-GEOD-62857 | biostudies-arrayexpress
Project description:To define what genes are predominantly or specifically expressed in either soma or germline in C. elegans adults, total RNA was extracted from germline-less glp-4 mutant animals or from dissected gonads, respectively.
2015-01-08 | GSE62857 | GEO
Project description:In C. elegans, the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2, are maternally deposited into the oocyte where they reprogram histone methylation to prevent somatic expression of germline genes. Here, we show that the progeny of spr-5; met-2 mutants display a severe developmental delay that is associated with the ectopic expression of germline genes targeted by the H3K36me2/3 methyltransferase, MES-4. Maternally deposited MES-4 maintains H3K36me2/3 at a subset of germline genes (hereafter referred to as MES-4 germline genes) in a transcription-independent manner, and this is required for germline proliferation in the subsequent generation. By performing ChIP-seq on L1 progeny from spr-5; met-2 mutants, we find that MES-4 germline genes ectopically accumulate H3K36me3 in somatic tissues. Additionally, knocking down MES-4 suppresses the ectopic expression of MES-4 germline genes and rescues the developmental delay. These data suggest a model where SPR-5, MET-2 and MES-4 carefully balance the inheritance of histone methylation from the parental germline to ensure the proper specification of germline versus soma in the progeny. Without SPR-5; MET-2 maternal reprogramming, somatic cells struggle to specify their proper cell fate amongst the background noise of inappropriate germline gene transcription, leading to a severe developmental delay.
2020-01-17 | GSE143837 | GEO
Project description:In C. elegans, the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2, are maternally deposited into the oocyte where they reprogram histone methylation to prevent somatic expression of germline genes. Here, we show that the progeny of spr-5; met-2 mutants display a severe developmental delay that is associated with the ectopic expression of germline genes targeted by the H3K36me2/3 methyltransferase, MES-4. Maternally deposited MES-4 maintains H3K36me2/3 at a subset of germline genes (hereafter referred to as MES-4 germline genes) in a transcription-independent manner, and this is required for germline proliferation in the subsequent generation. By performing ChIP-seq on L1 progeny from spr-5; met-2 mutants, we find that MES-4 germline genes ectopically accumulate H3K36me3 in somatic tissues. Additionally, knocking down MES-4 suppresses the ectopic expression of MES-4 germline genes and rescues the developmental delay. These data suggest a model where SPR-5, MET-2 and MES-4 carefully balance the inheritance of histone methylation from the parental germline to ensure the proper specification of germline versus soma in the progeny. Without SPR-5; MET-2 maternal reprogramming, somatic cells struggle to specify their proper cell fate amongst the background noise of inappropriate germline gene transcription, leading to a severe developmental delay.
2020-01-17 | GSE143838 | GEO