Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina.
Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina.
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DOI：
10.1016/j.exer.2016.11.013
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发表时间：
2017-01
影响因子：
3.4
通讯作者：
Lee TC
中科院分区：
文献类型：
--
作者：
Aparicio JG;Hopp H;Choi A;Mandayam Comar J;Liao VC;Harutyunyan N;Lee TC
来源于多能干细胞（PSC）的人视网膜神经节细胞（RGC）在人类疾病研究、药物筛选和治疗应用中具有预期的价值;然而，其全部潜力仍不充分。为了表征人胚胎干细胞（hESC）衍生的视网膜类器官中的RGC，我们检查了RGC标志物和表面抗原表达，并与人胎儿视网膜进行了比较。两种组织中的RGC均表现出CD 184和CD 171表达以及RGC标志物BRN 3和RBPMS的不同表达模式。视网膜类器官的视网膜祖细胞（RPC）表达CD 184，与其在胎儿视网膜成神经细胞层中的表达一致。在视网膜类器官中，CD 184表达在RGC感受态RPC中增强，并且在有丝分裂后的RGC前体上保留高CD 184表达;在成熟的RGC上检测到CD 171。CD 184和CD 171的差异表达时机允许从视网膜类器官中鉴定和富集处于从定向祖细胞到分化神经元的不同成熟状态的RGC。这些观察结果将促进分化期间PSC衍生的RGC的分子表征，这是建立这些体外产生的细胞的准确性的关键知识。此外，在视网膜类器官模型中进行的观察与在人胎儿视网膜中进行的观察密切平行，进一步验证了使用视网膜类器官来模拟早期视网膜发育。
Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its expression in the neuroblastic layer in fetal retina. In retinal organoids CD184 expression was enhanced in RGC competent RPCs and high CD184 expression was retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The differential expression timing of CD184 and CD171 permits identification and enrichment of RGCs from retinal organoids at differing maturation states from committed progenitors to differentiating neurons. These observations will facilitate molecular characterization of PSC-derived RGCs during differentiation, critical knowledge for establishing the veracity of these in vitro produced cells. Furthermore, observations made in the retinal organoid model closely parallel those in human fetal retina further validating use of retinal organoid to model early retinal development.