2. Academic Validation
  3. Breaking the link between morphology and potency for mESCs

Breaking the link between morphology and potency for mESCs

  • Cell Biosci. 2025 Oct 23;15(1):146. doi: 10.1186/s13578-025-01497-5.
Yixin Fan 1 2 3,  Xiaomin Wang 4,  Ziwei Zhai 4 5,  Tao Huang 4,  Wei Li 1 2 3,  Zechuan Liang 4,  Zhaoyi Ma 4,  Yu Fu 4,  Pengli Li 6,  Junqi Kuang 7 8,  Duanqing Pei 9 10
Affiliations

Affiliations

  • 1 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • 4 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.
  • 5 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong SAR, China.
  • 6 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences, Hong Kong SAR, China. pengli.li@hkisi.org.hk.
  • 7 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China. kuangjunqi@weatlake.edu.cn.
  • 8 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, Zhejiang, China. kuangjunqi@weatlake.edu.cn.
  • 9 Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China. peiduanqing@westlake.edu.cn.
  • 10 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, 310024, Zhejiang, China. peiduanqing@westlake.edu.cn.
PMID: 41131638 DOI: 10.1186/s13578-025-01497-5
Abstract

Background: In stem Cell Biology, a long-held structure-function relationship is the domed colony morphology and naïve pluripotency for mouse or human pluripotent stem cells. This link has provided a convenient way to recognize bona fide naïve pluripotent cells during derivation, passaging and characterization. However, the molecular basis of this link remains poorly understood.

Results: We show that a loss of domed morphology may not impact the overall genetic architecture of naïve pluripotency in mouse embryonic stem cells (mESCs). We first generated stable mESC lines by knocking out Myh9 that encodes non-muscle Myosin heavy chain IIA, resulting in colonies deprived of the typical domed morphology, but competent to differentiate into the three germ layers and chimeric mice. Modulating cell morphologies with inhibitors against kinases known to regulate Myosin pathway also phenocopy the knockout in wild type mESCs.

Conclusions: These results provide evidence that the domed morphology and potency can be uncoupled and suggest that domed structure is not a pre-requisite for acquiring and maintaining naïve pluripotency.

Keywords

Morphology; Mouse embryonic stem cell; Non-muscle myosin IIA; Pluripotency.

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