Functional Antagonism between Sall4 and Plzf Defines Germline Progenitors

SummaryTranscription factors required for formation of embryonic tissues often maintain their expression in adult stem cell populations, but whether their function remains equivalent is not clear. Here we demonstrate critical and distinct roles for Sall4 in development of embryonic germ cells and differentiation of postnatal spermatogonial progenitor cells (SPCs). In differentiating SPCs, Sall4 levels transiently increase and Sall4 physically interacts with Plzf, a transcription factor exclusively required for adult stem cell maintenance. Mechanistically, Sall4 sequesters Plzf to noncognate chromatin domains to induce expression of Kit, a target of Plzf-mediated repression required for differentiation. Plzf in turn antagonizes Sall4 function by displacing Sall4 from cognate chromatin to induce Sall1 expression. Taken together, these data suggest that transcription factors required for embryonic tissue development postnatally take on distinct roles through interaction with opposing factors, which hence define properties of the adult stem cell compartment.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (122 K)Download as PowerPoint slideHighlights► Sall4 is required for embryonic germ cell maintenance ► Differentiation of spermatogonial progenitor cells (SPCs) is Sall4 dependent ► Sall4 physically interacts with Plzf in SPCs ► Sall4 and Plzf antagonistically regulate Kit and Sall1 to define SPC function