Year: 2025
Type: article
Abstract: Decreased trabecular meshwork (TM) cellularity is a critical pathogenic cause of primary open-angle glaucoma, yet therapies to regenerate the decellularized TM are very limited. Induced pluripotent stem cell-derived TM-like cells (iPSC-TM) can efficiently restore aqueous humor outflow. Here, we conducted a multi-modal RNA sequencing analysis to characterize the molecular mechanisms underlying TM regeneration. Our clustering analysis identified a group of iPSC-derived alpha6 integrin-positive (iPSC-ITGA6 + ) cells with a distinct transcriptome that wasn’t observed in primary TM (pTM) cells. These iPSC-ITGA6 + cells not only stimulate pTM proliferation but also facilitate the repopulation of the TM and Schlemm’s canal in glaucoma, with a much higher efficiency than other iPSC-TM subtypes. Interaction with iPSC-ITGA6 + cells is characterized by the proliferation and rejuvenation of endogenous pTM cells, primarily through the transcription of long non-coding RNA nuclear paraspeckle assembly transcript1 and the abundance of paraspeckles within iPSC-ITGA6 + cells. Enhancing paraspeckle assembly by MEN β-associated RNA promotes the rejuvenation and proliferation of pTM, suggesting a novel and promising approach for TM regeneration.
Source: Nature Communications
Authors: Pengchao Feng, Chen Yu, Xiaoyan Zhang, Bin Xu, Shen Wu, Chen Xin, Sejiro Littleton, Jie Kang, Xiangji Wang, Shaoshuai Liang, Susu Chen, Wenyan Wang, Yanan Wang, Zhixin Yuan, Gaiping Xi, Xinhui Xing, Xinyu Ge, Zhishang Chang, Jinshan Tan, Jingxue Zhang, Bingqiang Zhang, Qilong Cao, Wenhua Xu, Markus H. Kuehn, Ningli Wang, Wei Zhu
Institutions: Qingdao University, Duke University, Duke Medical Center, Ocean University of China, Beijing Tongren Hospital, Capital Medical University, Beijing Institute for Brain Disorders, Haier Group (China), State Key Laboratory of Bio-Fibers and Eco-Textiles, Tsinghua University, University of Iowa, Iowa City VA Health Care System, Iowa City VA Medical Center
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4415583547