Transcription factor ZNF263 primes human embryonic stem cells for pluripotency dissolution and lineage commitment

Conventional human embryonic stem cells (hESCs) are capable of self-renewal and simultaneously poised for differentiation. But the mechanisms underlying this primed pluripotent state, which endows them with elevated responsiveness to differentiation cues, remain largely underexplored. Especially, little is known about the pivotal transcription factors (TFs) that orchestrate hESCs towards primed pluripotency. Here, we report a function of TF ZNF263 in pluripotency priming. Genetic and functional assays reveal that ZNF263 directly initiates the incipient expression of early differentiation genes and concurrently dampens the core pluripotency circuitry in hESCs, greatly tilting the balance from pluripotency maintenance to lineage priming. Importantly, ZNF263 deficiency markedly impairs pluripotency dissolution and multi-lineage differentiation in hESCs, particularly toward ectoderm. Moreover, single-cell transcriptomic profiling reveals that ZNF263 promotes the priming of cell fate commitment in hESCs, suggesting its indispensable requirement for pluripotency priming and lineage commitment continuum. Together, we demonstrate the role of ZNF263 in establishing the primed pluripotent state in hESCs and facilitating their differentiation into primary germ layer lineages.

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Publication Details

Journal
Nature Communications
Published
2025-11-05
DOI
https://doi.org/10.1038/s41467-025-64290-5
Primary Topic
Pluripotent Stem Cells Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Transcription factor ZNF263 primes human embryonic stem cells for pluripotency dissolution and lineage commitment

Xinbo Yuan, Zhaohui Gong, Hongduo Sun, Yi Arial Zeng et al.
Nature Communications
Pluripotent Stem Cells Research
article

Transcription factor ZNF263 primes human embryonic stem cells for pluripotency dissolution and lineage commitment

Xinbo Yuan, Zhaohui Gong, Hongduo Sun, Yi Arial Zeng, Naihe Jing, Qianqian Yin, Qingzhong Wang, Li Ruan, Shuhan Zhou, Yuangao Wang, Xin Liu, Haipeng Li, Peiyu Chen, Zhen Shao, Yana Li, Ji Wan, Jing Huang
article en

Abstract

Conventional human embryonic stem cells (hESCs) are capable of self-renewal and simultaneously poised for differentiation. But the mechanisms underlying this primed pluripotent state, which endows them with elevated responsiveness to differentiation cues, remain largely underexplored. Especially, little is known about the pivotal transcription factors (TFs) that orchestrate hESCs towards primed pluripotency. Here, we report a function of TF ZNF263 in pluripotency priming. Genetic and functional assays reveal that ZNF263 directly initiates the incipient expression of early differentiation genes and concurrently dampens the core pluripotency circuitry in hESCs, greatly tilting the balance from pluripotency maintenance to lineage priming. Importantly, ZNF263 deficiency markedly impairs pluripotency dissolution and multi-lineage differentiation in hESCs, particularly toward ectoderm. Moreover, single-cell transcriptomic profiling reveals that ZNF263 promotes the priming of cell fate commitment in hESCs, suggesting its indispensable requirement for pluripotency priming and lineage commitment continuum. Together, we demonstrate the role of ZNF263 in establishing the primed pluripotent state in hESCs and facilitating their differentiation into primary germ layer lineages.

Nature CommunicationsVol. 16(1)
Westlake University (CN), Guangzhou Experimental Station (CN), Shanghai Institute of Nutrition and Health (CN), Shanghai University of Traditional Chinese Medicine (CN), Center for Excellence in Molecular Cell Science (CN), University of Chinese Academy of Sciences (CN)
National Natural Science Foundation of China, Chinese Academy of Sciences, Tongji University, National Key Research and Development Program of China
Openalex Percentile: Top 71%
Pluripotent Stem Cells Research
DOIOpen Access PDFOpenAlex
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