Primitive to visceral endoderm maturation is essential for mouse epiblast survival beyond implantation

原始内胚层向内脏内胚层的成熟对于小鼠胚胎着床后的外胚层存活至关重要。

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作者:Antonia Weberling ,Dylan Siriwardena ,Christopher Penfold ,Neophytos Christodoulou ,Thorsten E Boroviak ,Magdalena Zernicka-Goetz

Abstract

The implantation of the mouse blastocyst initiates a complex sequence of tissue remodeling and cell differentiation events required for morphogenesis, during which the extraembryonic primitive endoderm transitions into the visceral endoderm. Through single-cell RNA sequencing of embryos at embryonic day 5.0, shortly after implantation, we reveal that this transition is driven by dynamic signaling activities, notably the upregulation of BMP signaling and a transient increase in Sox7 expression. Embryos deficient in Hepatocyte nuclear factor-1-beta (Hnf1b-/-), a gene critical for visceral endoderm differentiation, showed an interaction between visceral endoderm and epiblast, crucial for epiblast survival. Single-cell RNA profiling of Hnf1b-/- visceral endoderm shows developmental delays and severe dysregulation in several nutrient transport pathways. Impaired glucose uptake in Hnf1b-/- embryos suggests that the activation of nutrient transport mechanisms during the primitive-to-visceral endoderm transition may be vital for post-implantation epiblast development. These findings offer new insights into the molecular regulation of early mammalian development. Keywords: Biological sciences; Cell biology; Developmental biology; Embryology; Natural sciences.

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