BRIEF RESEARCH REPORT article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1609826
This article is part of the Research TopicModeling Organogenesis: Advancements in Three-Dimensional Stem Cell Differentiation and Disease ApplicationsView all articles
Molecular Analysis of RAX2-Regulated Retinal Development Using Human Retinal Organoids at a Single-cell Resolution
Provisionally accepted
- 1Senior Department of Ophthalmology, 3rd medical center of Chinese PLA General Hospital, Beijing, China
- 2State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- 3Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, China
- 4State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sci-ences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Human embryonic stem cells (hESC)-derived retinal organoids are sophisticated in vitro systems for dissecting the complex dynamics of human retinal development. The formation of the human retina is a precisely organized process that depends on the regulated differentiation of retinal progenitor cells; however, many of the basic mechanisms remain to be explored. Here, using hESC-derived retinal organoids, we elucidated the temporal contribution of RAX2 to retinal development, with an emphasis on photoreceptor cells (PC) formation. The results were corroborated using human fetal retinal tissue at various gestational ages. Using CRISPR/Cas9-mediated gene knockout, we delineated the essential role of RAX2 in modulating PC specifications. RAX2 deficiency significantly altered the expression of PAX6 and SOX2, two essential regulators of retinogenesis. Our results suggested that RAX2 is significant in retinal development, underpinning its potential as a therapeutic target in related retinal disorders.
Keywords: human embryonic stem cells (hESC), Retinal organoid, retinal development, Photoreceptor Cells, ScRNA-seq
Received: 11 Apr 2025; Accepted: 28 May 2025.
Copyright: © 2025 Wang, Sun, Na, HUANG and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
YUE HUANG, State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sci-ences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Guang Liu, State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sci-ences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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