GASZ promotes germ cell derivation from embryonic stem cells

Abstract

Primordial germ cells (PGCs) are the first germ-line population that forms from the proximal epiblast of the developing embryo. Despite their biological importance, the regulatory networks whereby PGCs arise, migrate, and differentiate into gametes during embryonic development remains elusive, largely due to the limited number of germ cells in the early embryo. To elucidate the molecular mechanisms that govern early germ cell development, we utilized an in vitro differentiation model of embryonic stem cells (ESCs) and screened a series of candidate genes with specific expression in the adult reproductive organs. We discovered that gain of function of Gasz, a gene previously reported to participate in meiosis of postnatal spermatocytes, led to the most robust upregulation of PGC formation from both human and murine ESCs. In contrast, Gasz deficiency resulted in pronounced reduction of germ cells during ESC differentiation and decreased expression of MVH and DAZL in genital ridges during early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key germ cell regulator, to synergistically promote germ cell derivation from ESCs. Thus, our data reveal a potential role of GASZ during embryonic germ cell development and provide a powerful in vitro system for dissecting the molecular pathways in early germ cell formation during embryogenesis.

CD71high population represents primitive erythroblasts derived from mouse embryonic stem cells

“…Cell culture and ESC differentiation Mouse ESCs were cultured on irradiated MEFs as previously described (Wang et al, 2013). For EB formation, dissociated ESCs were plated to allow MEFs to adhere in IMDM/15% FBS (Invitrogen) with 0.2 mg/ml iron-saturated transferrin (Calbiochem), 4.5 mM α-monothiolglycerol (MTG, Sigma), and 50 μg/ml ascorbic acid (Sigma).…”

“…Real-time PCR was performed on a Stratagene MX3000P instrument and analyzed as described previously (Wang et al, 2013). Primers are listed in Supplementary Table S1.…”

A Novel Role of CDX1 in Embryonic Epicardial Development

“…IF and hematoxylin/eosin histological analyses were performed following a published protocol [19]. All IHF was performed on 4 µm frozen sections.…”

Interplay of transcription factors and microRNAs during embryonic hematopoiesis

“…Real-time PCR was performed on a Stratagene MX3000P instrument and analyzed as described previously (Wang et al, 2013). Primers used in this study are listed in Table S1 in Supporting Information.…”