A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells

Haipeng Fu, Tingyu Wang, Xiaohui Kong, Kun Yan, Yang Yang, Jingyi Cao, Yafei Yuan, Nan Wang, Kehkooi Kee, Zhi John Lu and Qiaoran Xi ()
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Haipeng Fu: Tsinghua University
Tingyu Wang: Tsinghua University
Xiaohui Kong: Tsinghua University
Kun Yan: Tsinghua University
Yang Yang: Tsinghua University
Jingyi Cao: Tsinghua University
Yafei Yuan: Tsinghua University
Nan Wang: Tsinghua University
Kehkooi Kee: Tsinghua University
Zhi John Lu: Tsinghua University
Qiaoran Xi: Tsinghua University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract TGF-β family proteins including Nodal are known as central regulators of early development in metazoans, yet our understanding of the scope of Nodal signaling’s downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we identified a highly conserved, transmembrane micropeptide—NEMEP—as a direct target of Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells (mESCs), and this micropeptide is essential for mesendoderm differentiation. We showed that NEMEP interacts with the glucose transporters GLUT1/GLUT3 and promotes glucose uptake likely through these interactions. Thus, beyond expanding the scope of known Nodal signaling targets in early development and showing that this target micropeptide augments the glucose uptake during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered glucose metabolism on cell fate determination.

Date: 2022
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DOI: 10.1038/s41467-022-31762-x

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