A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-06-10 Epub Date: 2025-05-22 DOI:10.1016/j.stemcr.2025.102508

Brian W Basinski, Yuanhao Huang, Qiang Li, Charukesi D Sivakumar, Tyler J Carman, Hana M Pan, Jing Xu, D Ford Hannum, Jie Liu, Rajesh C Rao

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Abstract

The transcriptional regulation underlying eye field (retinal primordium) development requires precise control, yet the mechanisms guiding lineage-specific differentiation within the central nervous system (CNS) remain incompletely understood. Using neuroectoderm (NE) organoids derived from mouse embryonic stem cells, we investigate the role of PRDM13 in eye field specification. We demonstrate that Prdm13 expression inhibits RX⁺ eye field fate but permits non-eye field NE differentiation, an effect that depends on its first and second zinc-finger domains. Prdm13 activates the WNT/β-catenin signaling pathway during differentiation, leading to downregulation of key transcription factors crucial for establishing the eye field. Pharmacological inhibition of WNT signaling abolishes PRDM13-mediated suppression, restoring RX⁺ eye field differentiation. Our work reveals a previously undescribed PRDM13-WNT signaling axis that regulates lineage-specific neural differentiation of embryonic stem cells.

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锌指依赖、prdm13驱动的机制通过WNT信号调节小鼠胚胎干细胞的视网膜祖细胞命运。

视野（视网膜原基）发育的转录调控需要精确的控制，但中枢神经系统（CNS）中指导谱系特异性分化的机制仍然不完全清楚。利用来源于小鼠胚胎干细胞的神经外胚层（NE）类器官，我们研究了PRDM13在视野规范中的作用。我们证明，Prdm13表达抑制RX+视野命运，但允许非视野NE分化，这种影响取决于其第一和第二锌指结构域。Prdm13在分化过程中激活WNT/β-catenin信号通路，导致对建立视野至关重要的关键转录因子下调。药理抑制WNT信号可消除prdm13介导的抑制，恢复RX+视野分化。我们的工作揭示了先前未描述的PRDM13-WNT信号轴，该信号轴调节胚胎干细胞谱系特异性神经分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.