Abstract

Germ cell specification in mice, which generates primordial germ cells (PGCs), the common source of the oocytes and spermatozoa, from the epiblast, integrates three key events: repression of the somatic program, re-acquisition of potential pluripotency, and genome-wide epigenetic reprogramming. A PR-domain containing protein, Blimp1 (also known as Prdm1), has been identified as a critical factor for PGC specification. Using a highly representative single-cell microarray technology, we identified a complex but highly ordered genome-wide transcription dynamics associated with PGC specification. This analysis not only demonstrated a dominant role of Blimp1 for the repression of the genes normally down-regulated in PGCs relative to their somatic neighbors, but also revealed the presence of gene expression programs initiating independently from Blimp1. Among such programs, we identified Prdm14, another PR-domain containing protein, as a key regulator for the re-acquisition of potential pluripotency and genome-wide epigenetic reprogramming. The launch of the germ cell lineage in mice, therefore, is orchestrated by two independently acquired, PR domain-containing transcriptional regulators, Blimp1 and Prdm14.

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