A case for revisiting Nodal signaling in human pluripotent stem cells,STEM CELLS

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A case for revisiting Nodal signaling in human pluripotent stem cells
STEM CELLS ( IF 4.0 ) Pub Date : 2021-05-01 , DOI: 10.1002/stem.3383
Kevin Hayes ₁ , Yun-Kyo Kim ₁ , Martin F Pera ₁

Affiliation

Nodal is a transforming growth factor-β (TGF-β) superfamily member that plays a number of critical roles in mammalian embryonic development. Nodal is essential for the support of the peri-implantation epiblast in the mouse embryo and subsequently acts to specify mesendodermal fate at the time of gastrulation and, later, left-right asymmetry. Maintenance of human pluripotent stem cells (hPSCs) in vitro is dependent on Nodal signaling. Because it has proven difficult to prepare a biologically active form of recombinant Nodal protein, Activin or TGFB1 are widely used as surrogates for NODAL in hPSC culture. Nonetheless, the expression of the components of an endogenous Nodal signaling pathway in hPSC provides a potential autocrine pathway for the regulation of self-renewal in this system. Here we review recent studies that have clarified the role of Nodal signaling in pluripotent stem cell populations, highlighted spatial restrictions on Nodal signaling, and shown that Nodal functions in vivo as a heterodimer with GDF3, another TGF-β superfamily member expressed by hPSC. We discuss the role of this pathway in the maintenance of the epiblast and hPSC in light of these new advances.

中文翻译：

重新审视人类多能干细胞中节点信号传导的案例

Nodal 是一种转化生长因子-β (TGF-β) 超家族成员，在哺乳动物胚胎发育中发挥着许多关键作用。Nodal 对于支持小鼠胚胎中的着床周围外胚层至关重要，并随后在原肠胚形成时起到指定中内胚层命运的作用，然后是左右不对称。体外人多能干细胞 (hPSC) 的维持依赖于 Nodal 信号传导。由于已证明难以制备具有生物活性形式的重组节点蛋白，因此激活素或 TGFB1 被广泛用作 hPSC 培养中 NODAL 的替代物。尽管如此，hPSC 中内源性 Nodal 信号通路成分的表达为该系统中自我更新的调节提供了潜在的自分泌途径。在这里，我们回顾了最近的研究，这些研究阐明了 Nodal 信号传导在多能干细胞群中的作用，强调了 Nodal 信号传导的空间限制，并表明 Nodal 在体内作为 GDF3 的异二聚体发挥作用，GDF3 是由 hPSC 表达的另一个 TGF-β 超家族成员。鉴于这些新进展，我们讨论了该途径在维持外胚层和 hPSC 中的作用。

更新日期：2021-05-01

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