Luo Ziming, Shah Sahil, Tanasa Bogdan, Chang Kun-Che, Goldberg Jeffrey L
Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
iScience. 2024 May 24;27(6):110100. doi: 10.1016/j.isci.2024.110100. eCollection 2024 Jun 21.
Retinal ganglion cell (RGC) differentiation is tightly controlled by extrinsic and intrinsic factors. Growth and differentiation factor 15 (GDF-15) promotes RGC differentiation, opposite to GDF-11 which inhibits RGC differentiation, both in the mouse retina and in human stem cells. To deepen our understanding of how these two closely related molecules confer opposing effects on retinal development, here we assess the transcriptional profiles of mouse retinal progenitors exposed to exogenous GDF-11 or -15. We find a dichotomous effect of GDF-15 on RGC differentiation, decreasing RGCs expressing residual pro-proliferative genes and increasing RGCs expressing non-proliferative genes, suggestive of greater RGC maturation. Furthermore, GDF-11 promoted the differentiation of photoreceptors and amacrine cells. These data enhance our understanding of the mechanisms underlying the differentiation of RGCs and photoreceptors from retinal progenitors and suggest new approaches to the optimization of protocols for the differentiation of these cell types.
视网膜神经节细胞(RGC)的分化受到外在和内在因素的严格控制。在小鼠视网膜和人类干细胞中,生长分化因子15(GDF-15)促进RGC分化,而GDF-11则抑制RGC分化,二者作用相反。为了更深入地了解这两种密切相关的分子如何对视网膜发育产生相反的影响,我们在此评估了暴露于外源性GDF-11或-15的小鼠视网膜祖细胞的转录谱。我们发现GDF-15对RGC分化有二分效应,减少表达残留增殖相关基因的RGC数量,增加表达非增殖相关基因的RGC数量,这表明RGC成熟度更高。此外,GDF-11促进了光感受器和无长突细胞的分化。这些数据加深了我们对视网膜祖细胞分化为RGC和光感受器的潜在机制的理解,并为优化这些细胞类型分化方案提供了新方法。