Induction of meiosis by embryonic gonadal somatic cells differentiated from pluripotent stem cells

Haiying Wang; Linlin Liu; Chang Liu; Lingling Wang; Jiyu Chen; Huasong Wang; Dai Heng; Ming Zeng; Chun Liu; Zhongcheng Zhou; Xiaoying Ye; Yajuan Wan; Huiyu Li; Lin Liu

doi:10.1186/s13287-021-02672-4

Induction of meiosis by embryonic gonadal somatic cells differentiated from pluripotent stem cells

Stem Cell Res Ther. 2021 Dec 20;12(1):607. doi: 10.1186/s13287-021-02672-4.

Authors

Haiying Wang^{1

2}, Linlin Liu^{1

2}, Chang Liu^{1

2}, Lingling Wang^{1

2}, Jiyu Chen^{1

2}, Huasong Wang³, Dai Heng^{1

2}, Ming Zeng⁴, Chun Liu^{1

2}, Zhongcheng Zhou⁵, Xiaoying Ye^{1

2}, Yajuan Wan¹, Huiyu Li^{1

2}, Lin Liu^{6

7

8}

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
² Department of Cell Biology and Genetics, College of Life Sciences; The Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China.
³ Department of Cell Biology, College of Life Sciences, Tsinghua University, Beijing, 100084, China.
⁴ Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁵ Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510655, China.
⁶ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.
⁷ Department of Cell Biology and Genetics, College of Life Sciences; The Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.
⁸ The Key Laboratory of Bioactive Materials Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China. liulin@nankai.edu.cn.

Abstract

Background: Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ cell like cells (PGCLCs) from pluripotent stem cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells.

Methods: We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells.

Results: Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5_gonadal somatic cells (E12.5_GSCs). Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5_GSC-like cells (E12.5_GSCLCs). After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5_GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility.

Conclusion: ESCs can be induced into embryonic gonadal somatic cell like cells by small molecules.

Keywords: ESCs; Female infertility; GSCLCs; Meiosis; Small molecules.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Embryonic Stem Cells
Female
Germ Cells
Meiosis
Mice
Oocytes / metabolism
Pluripotent Stem Cells*