We need your help! If you've ever found our data helpful, please take our impact survey (15 min). Your replies will help keep the data flowing to the scientific community. Please Click here for Survey


Dataset Information


In vitro expansion of mouse primordial germ cell-like cells recapitulates an epigenetic blank slate.

ABSTRACT: The expansion of primordial germ cells (PGCs), the precursors for the oocytes and spermatozoa, is a key challenge in reproductive biology/medicine. Using a chemical screening exploiting PGC-like cells (PGCLCs) induced from mouse embryonic stem cells (ESCs), we here identify key signaling pathways critical for PGCLC proliferation. We show that the combinatorial application of Forskolin and Rolipram, which stimulate cAMP signaling via different mechanisms, expands PGCLCs up to ~50-fold in culture. The expanded PGCLCs maintain robust capacity for spermatogenesis, rescuing the fertility of infertile mice. Strikingly, during expansion, PGCLCs comprehensively erase their DNA methylome, including parental imprints, in a manner that precisely recapitulates genome-wide DNA demethylation in gonadal germ cells, while essentially maintaining their identity as sexually uncommitted PGCs, apparently through appropriate histone modifications. By establishing a paradigm for PGCLC expansion, our system reconstitutes the epigenetic "blank slate" of the germ line, an immediate precursory state for sexually dimorphic differentiation.


PROVIDER: S-EPMC5494472 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

| GSE87645 | GEO
| GSE87644 | GEO
1000-01-01 | S-EPMC5775501 | BioStudies
1000-01-01 | S-EPMC4825550 | BioStudies
2020-01-01 | S-EPMC7055065 | BioStudies
2017-01-01 | S-EPMC5666620 | BioStudies
2016-01-01 | S-EPMC5003264 | BioStudies
2016-01-01 | S-EPMC5145290 | BioStudies
2016-01-01 | S-EPMC4724940 | BioStudies
1000-01-01 | S-EPMC5803789 | BioStudies