Multilayered control of retinal stem/progenitor cell fate in the single-cell and organoid era: Developmental blueprints and regenerative opportunities

作者：Qifei Xie, Mei Zeng, Liwei Mao, Shichao Han, Da Sun, Zhi Zheng · 发表于：World Journal of Stem Cells · 年份：2026 · DOI：10.4252/wjsc.v18.i4.118621 · 被引用次数：1

Irreversible degeneration of retinal neurons and the retinal pigment epithelium is a major cause of vision loss, and current pharmacological or surgical treatments seldom rebuild lost tissue, placing stem cell-based regeneration at the center of therapeutic exploration. Retinal progenitor cells, Müller glia (MG)-derived progenitors, pluripotent stem cell-derived retinal pigment epithelium and photoreceptors, and emerging human retinal stem cell candidates together provide a diverse cellular repertoire whose behavior is governed by tightly coordinated fate-control mechanisms. Enabled by single-cell and spatial multi-omics in developing human retina and retinal organoids, these mechanisms can now be mapped at unprecedented resolution, revealing how distinct lineage trajectories and molecular states arise. This review synthesizes a multilayered framework of fate regulation encompassing the diversity and plasticity of embryonic progenitors, MG-derived progenitors, ciliary margin-like cells and putative adult retinal stem cells, and examines how transcription factor hierarchies, epigenetic landscapes, and non-coding RNAs interact with translational, metabolic and inflammatory cues to shape competence windows and photoreceptor vs inner retinal fates in development and disease. These insights are then connected to next-generation regenerative strategies, including engineered retinal organoids and sheets, MG reprogramming, and rational combinations of gene and cell therapies designed...