Molecular Control of Retinal Ganglion Cell Specification and Differentiation

Xiang, Mengqing; Jiang, Hongzhi; Jin, Kangxin; Qiu, Feng

doi:10.5772/19832

Cited by 3 publications

(4 citation statements)

References 89 publications

(151 reference statements)

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“…In retinal organoids BRN3+ cells were abundant at day 27 while RBPMS+ cells were rare; however, RBPMS cells became abundant at later ages, consistent with BRN3 being a transcription factor required early to specify RGC development and RBPMS functioning in a differentiating cell (Hörnberg et al, 2013; Mu et al, 2005; Xiang et al, 2011) (Figure 3A). Interestingly, in retinal organoids relatively few cells appeared to co-stain for BRN3 and RBPMS; however, upon close inspection in all RBPMS+ cells BRN3 signal was detected, albeit weakly compared to many BRN3+ cells.…”

Section: Resultssupporting

confidence: 54%

“…The ATOH7+ cell population overlaps with BRN3+ cells that were also primarily observed in the emergent basal layer. This pattern is expected of ATOH7+ RPCs that mature first to BRN3+ ATOH7+ RGC precursors, and then to BRN3+, ATOH7− RGCs (Fu et al, 2009; Xiang et al, 2011). …”

Section: Resultsmentioning

confidence: 68%

“…To characterize RGCs in the retinal organoids we evaluated expression of the common molecular markers ATOH7 (MATH5), which identifies RGC competent RPCs as well as early post-mitotic RGCs, and BRN3 (BRN3a-c, POU4f1-3), which is a family of transcription factors required for RGC differentiation (Figure 2A) (Brown et al, 2001; Mu et al, 2005; Wang et al, 2001; Xiang et al, 2011; Yang et al, 2003). In retinal organoids ATOH7+ cells were first detected by day 27 and observed interspersed in the neuroblastic layer (NBL) as retinal organoids mature.…”

Section: Resultsmentioning

confidence: 99%

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Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina

Aparicio

Hopp

Choi

et al. 2017

Experimental Eye Research

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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.

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

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Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina

Aparicio

Hopp

Choi

et al. 2017

Experimental Eye Research

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“…The Pou4f1 knockout mice die at birth due to severe defects in RGCs 52,53 . In the adult mouse retina, Pou4f1 localizes in more than 70% of RGCs.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic control of neural differentiation in Opto‐mGluR6 engineered retinal pigment epithelial cell line and mesenchymal stem cells

Najafabadi

Sadeghi

Zibaii

et al. 2021

J of Cellular Biochemistry

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In retinal degenerative disorders, when neural retinal cells are damaged, cell transplantation is one of the most promising therapeutic approaches. Optogenetic technology plays an essential role in the neural differentiation of stem cells via membrane depolarization. This study explored the efficacy of blue light stimulation in neuroretinal differentiation of Opto‐mGluR6‐engineered mouse retinal pigment epithelium (mRPE) and bone marrow mesenchymal stem cells (BMSCs). mRPE and BMSCs were selected for optogenetic study due to their capability to differentiate into retinal‐specific neurons. BMSCs were isolated and phenotypically characterized by the expression of mesenchymal stem cell‐specific markers, CD44 (99%) and CD105 (98.8%). mRPE culture identity was confirmed by expression of RPE‐specific marker, RPE65, and epithelial cell marker, ZO‐1. mRPE cells and BMSCs were transduced with AAV‐MCS‐IRES‐EGFP‐Opto‐mGluR6 viral vector and stimulated for 5 days with blue light (470 nm). RNA and protein expression of Opto‐mGluR6 were verified. Optogenetic stimulation‐induced elevated intracellular Ca2+ levels in mRPE‐ and BMS‐treated cells. Significant increase in cell growth rate and G1/S phase transition were detected in mRPE‐ and BMSCs‐treated cultures. Pou4f1, Dlx2, Eomes, Barlh2, Neurod2, Neurod6, Rorb, Rxrg, Nr2f2, Ascl1, Hes5, and Sox8 were overexpressed in treated BMSCs and Barlh2, Rorb, and Sox8 were overexpressed in treated mRPE cells. Expression of Rho, Thy1, OPN1MW, Recoverin, and CRABP, as retinal‐specific neuron markers, in mRPE and BMS cell cultures were demonstrated. Differentiation of ganglion, amacrine, photoreceptor cells, and bipolar and Muller precursors were determined in BMSCs‐treated culture and were compared with mRPE. mRPE cells represented more abundant terminal Muller glial differentiation compared with BMSCs. Our results also demonstrated that optical stimulation increased the intracellular Ca2+ level and proliferation and differentiation of Opto‐mGluR6‐engineered BMSCs. It seems that optogenetic stimulation of mRPE‐ and BMSCs‐engineered cells would be a potential therapeutic approach for retinal degenerative disorders.

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