Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

We asked whether telomere shortening impairs differentiation of ESCs into germ cell lineage. Terc-/- ESCs were used to investigate the effects of short telomeres on germ cell specification by in vitro differentiation. Short telomeres greatly reduced induction of PGCLCs from ESCs. Mechanistically, short telomeres resulted in excessive chromatin accessibility, which in turn activated the genes regulated by chromatin. Notably, Fst overexpression reduced BMP-Smad signaling and thus induction of PGCLCs, meanwhile upregulation of MAPK signaling pathway increase somatic lineage differentiation in short telomeres sampels. Moreover, knockin of Terc gene by CRISPR/Cas9 in Terc-/- ESCs restored telomere length and normal gene expression profile, and rescued PGCLC induction, revealing important roles of telomeres in PGC fate decision. We used long telomere (LT), short telomere (LT) and telomere length rescued (RT) 1dEBs, PGCLCs and 1dMeiLCs differention from ESCs to do ATAC-seq for analysis the chromatin accessibility of global genome, PGC genes, somatic lineage genes, meiosis-related genes and genes invovled in MAPK and TGF-beta signaling pathways.