Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes

Qi-Hua HUA; Xuechun ZHANG; Ruifeng TIAN; Zhigang SHE; Zan HUANG

doi:10.1631/jzus.B2400127

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Review | Updated：2025-09-22

Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes
Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes
核内有丝分裂：细胞周期中的新细胞命运—以巨核细胞和肝细胞的多倍体化为例
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 9, Pages: 843-862(2025)
Affiliations：

1.College of Life Sciences, Key Laboratory of Cell Homeostasis of Hubei Province, Wuhan University, Wuhan 430060, China
2.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3.Gannan Innovation and Translational Medicine Research Institute, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China
Funds：
DOI：10.1631/jzus.B2400127
CLC：
CSTR：
Received：07 March 2024，

Revised：2024-08-31，

Published：20 September 2025
Accepted：

花启华,张雪纯,田瑞锋等.核内有丝分裂：细胞周期中的新细胞命运—以巨核细胞和肝细胞的多倍体化为例[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(09):843-862.

Qi-Hua HUA, Xuechun ZHANG, Ruifeng TIAN, et al. Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(9): 843-862.
花启华,张雪纯,田瑞锋等.核内有丝分裂：细胞周期中的新细胞命运—以巨核细胞和肝细胞的多倍体化为例[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(09):843-862. DOI： 10.1631/jzus.B2400127.

Qi-Hua HUA, Xuechun ZHANG, Ruifeng TIAN, et al. Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(9): 843-862. DOI： 10.1631/jzus.B2400127.

摘要

巨核细胞和肝细胞在哺乳动物中具有独特性，它们在终末分化过程中通过核内有丝分裂实现多倍体化。许多多倍体化的调控因子和潜在机制已被报道，其中大多数与发育、器官发生和细胞分化紧密相关。然而，核内有丝分裂的本质尚未完全阐明，该过程包括成功进入和退出有丝分裂而不发生完全的胞质分裂。本文强调，核内有丝分裂是细胞周期中一种新的细胞命运，而四倍体阶段则是细胞命运决定的关键时期。本文综述了该领域的最新研究进展，并为细胞如何操控有丝分裂以实现核内有丝分裂提供了新见解，即核内有丝分裂细胞能够规避四倍体检查点的限制，继续进行多次全基因组加倍。这些发现不仅加深了我们对核内有丝分裂作为一种基本生物学过程的理解，还为多倍体化的生理和病理学意义提供了新的视角。

Abstract

Megakaryocytes and hepatocytes are unique cells in mammals that undergo polyploidization through endomitosis in terminal differentiation. Many polyploidization regulators and underlying mechanisms have been reported

most of which are tightly coupled with development

organogenesis

and cell differentiation. However

the nature of endomitosis

which involves successful entry into and exit from mitosis without complete cytokinesis

has not yet been fully elucidated. We highlight that endomitosis is a new cell fate in the cell cycle

and tetraploidy is a critical stage at the bifurcation of cell fate decision. This review summarizes the recent research progress in this area and provides novel insights into how cells manipulate mitosis toward endomitosis. Endomitotic cells can evade the tetraploidy restrictions and proceed to multiple rounds of the cell cycle. This knowledge not only deepens our understanding of endomitosis as a fundamental biological process but also offers new perspectives on the physiological and pathophysiological implications of polyploidization.

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