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

Mengyi Wei; Yanglin Chen; Chaoyue Zhao; Li Zheng; Baojiang Wu; Chen Chen; Xihe Li; Siqin Bao

doi:10.3389/fcell.2021.713503

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

Front Cell Dev Biol. 2021 Aug 5:9:713503. doi: 10.3389/fcell.2021.713503. eCollection 2021.

Authors

Mengyi Wei^{1

2}, Yanglin Chen^{1

2

3}, Chaoyue Zhao^{1

2}, Li Zheng^{1

2}, Baojiang Wu^{1

2}, Chen Chen^{1

2}, Xihe Li^{1

2

4}, Siqin Bao^{1

2}

Affiliations

¹ State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China.
² Institute of Animal Genetic Research of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, China.
³ School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
⁴ Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot, China.

Abstract

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.

Keywords: Activin A; LIF; conversion; embryonic stem cells; primed stem cells.