4.7 Article

Establishment of Mouse Primed Stem Cells by Combination of Activin and LIF Signaling

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出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.713503

关键词

primed stem cells; embryonic stem cells; conversion; Activin A; LIF

资金

  1. Inner Mongolia Autonomous Region Science and Technology Plan of China [2020ZD0007]
  2. National Natural Science Foundation of China [32060176]

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A study successfully derived a primed stem cell line that can be reversed to a naive state under specific conditions. This finding is important for understanding the control of pluripotency fate and conversion between different states.
In mice, embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are established from pre- and post-implantation embryos and represent the naive and primed state, respectively. Herein we used mouse leukemia inhibitory factor (LIF), which supports ESCs self-renewal and Activin A (Act A), which is the main factor in maintaining EpiSCs in post-implantation epiblast cultures, to derive a primed stem cell line named ALSCs. Like EpiSCs, ALSCs express key pluripotent genes Oct4, Sox2, and Nanog; one X chromosome was inactivated; and the cells failed to contribute to chimera formation in vivo. Notably, compared to EpiSCs, ALSCs efficiently reversed to ESCs (rESCs) on activation of Wnt signaling. Moreover, we also discovered that culturing EpiSCs in AL medium for several passages favored Wnt signaling-driven naive pluripotency. Our results show that ALSCs is a primed state stem cell and represents a simple model to study the control of pluripotency fate and conversion from the primed to the naive state.

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