Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells

Khalili, Saeed; Ballios, Brian G.; Belair-Hickey, Justin; Donaldson, Laura; Liu, Jeff; Coles, Brenda L.K.; Grisé, Kenneth N.; Baakdhah, Tahani; Bader, Gary D.; Wallace, Valerie A.; Bernier, Gilbert; Shoichet, Molly S.; Kooy, Derek van der

doi:10.1016/j.scr.2018.11.005

Cited by 12 publications

(12 citation statements)

References 41 publications

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“…To properly establish differentiation will be the goal of future studies and will require much more in-depth characterization of Msx1 -tdTomato + cells using multiple cell-specific markers, genetic reporters, single cell RNAseq and functional assays, like electrophysiology. In addition, prior studies in the post-hatch chick ciliary marginal zone have shown that different exogenous growth factors result in different types of cells produced by retinal progenitors at the CMZ [ 85 ], while our lab has demonstrated that exogenous factors can be used to influence the cell fate specification of retinal stem and progenitor cells in vitro [ 5 , 6 ]. Therefore, it is possible that different combinations of FINS components and/or injury could bias differentiation to particular cell types in the adult mammalian CE but this is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…The pigmented ciliary epithelium (CE) in the adult mammalian eye harbours a rare subpopulation of retinal stem cells (RSCs) that are capable of clonal expansion, self-renewal, and differentiation into all the cell types of the retina when isolated in vitro. [ 1 – 6 ]. The CE is an epithelial bilayer that overlays the ciliary body and is contiguous with the peripheral retina and retinal pigmented epithelium (RPE) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2

et al. 2021

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Background The adult mammalian retina does not have the capacity to regenerate cells lost due to damage or disease. Therefore, retinal injuries and blinding diseases result in irreversible vision loss. However, retinal stem cells (RSCs), which participate in retinogenesis during development, persist in a quiescent state in the ciliary epithelium (CE) of the adult mammalian eye. Moreover, RSCs retain the ability to generate all retinal cell types when cultured in vitro, including photoreceptors. Therefore, it may be possible to activate endogenous RSCs to induce retinal neurogenesis in vivo and restore vision in the adult mammalian eye. Methods To investigate if endogenous RSCs can be activated, we performed combinatorial intravitreal injections of antagonists to BMP and sFRP2 proteins (two proposed mediators of RSC quiescence in vivo), with or without growth factors FGF and Insulin. We also investigated the effects of chemically-induced N-methyl-N-Nitrosourea (MNU) retinal degeneration on RSC activation, both alone and in combination withthe injected factors. Further, we employed inducible Msx1-CreERT2 genetic lineage labeling of the CE followed by stimulation paradigms to determine if activated endogenous RSCs could migrate into the retina and differentiate into retinal neurons. Results We found that in vivo antagonism of BMP and sFRP2 proteins induced CE cells in the RSC niche to proliferate and expanded the RSC population. BMP and sFRP2 antagonism also enhanced CE cell proliferation in response to exogenous growth factor stimulation and MNU-induced retinal degeneration. Furthermore, Msx1-CreERT2 genetic lineage tracing revealed that CE cells migrated into the retina following stimulation and/or injury, where they expressed markers of mature photoreceptors and retinal ganglion cells. Conclusions Together, these results indicate that endogenous adult mammalian RSCs may have latent regenerative potential that can be activated by modulating the RSC niche and hold promise as a means for endogenous retinal cell therapy to repair the retina and improve vision.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2

et al. 2021

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“…Moreover, rod and cone photoreceptors share overlapping differentiation sequences. Taurine and retinoic acid promote differentiation into rodrestricted progenitors (77). Similar to RPE cells, xenofree differentiation protocols for photoreceptors have also been developed (66).…”

Section: Photoreceptor Cellsmentioning

confidence: 99%

Pluripotent stem cell therapy for retinal diseases

Ahmed¹,

Johnston²,

Singh³

2021

Ann Transl Med

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Pluripotent stem cells (PSCs), which include human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSC), have been used to study development of disease processes, and as potential therapies in multiple organ systems. In recent years, there has been increasing interest in the use of PSCbased transplantation to treat disorders of the retina in which retinal cells have been functionally damaged or lost through degeneration. The retina, which consists of neuronal tissue, provides an excellent system to test the therapeutic utility of PSC-based transplantation due to its accessibility and the availability of highresolution imaging technology to evaluate effects. Preclinical trials in animal models of retinal diseases have shown improvement in visual outcomes following subretinal transplantation of PSC-derived photoreceptors or retinal pigment epithelium (RPE) cells. This review focuses on preclinical studies and clinical trials exploring the use of PSCs for retinal diseases. To date, several phase I/II clinical trials in patients with agerelated macular degeneration (AMD) and Stargardt disease (STGD1) have demonstrated the safety and feasibility of PSC-derived RPE transplantation. Additional phase I/II clinical trials using PSC-derived RPE or photoreceptor cells for the treatment of AMD, STGD1, and also retinitis pigmentosa (RP) are currently in the pipeline. As this field continues to evolve, additional technologies may enhance PSC-derived cell transplantation through gene-editing of autologous cells, transplantation of more complex cellular structures such as organoids, and monitoring of transplanted cells through novel imaging technologies.

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“…encoding barcodes, histological markers and fluorescent proteins) into the host genome and thus are very useful for lineage tracing. Clonal resolution is achieved by sparse labeling of locally restricted clones, such as in the retina (Khalili et al, 2018;Turner and Cepko, 1987;Fields-Berry et al, 1992), or multiple rounds of infection followed by barcode sequencing, which is more efficient for retrieving clonal information than sequencing for integration sites (Adair et al, 2020). Combined with laser capture microscopy for spatially distinct cell populations, barcode sequencing can provide highly complex lineage information through multiple infection with up to 10 5 tags.…”

Section: Retroviral Clonal Analysismentioning

confidence: 99%

Neural crest lineage analysis: from past to future trajectory

Tang

Bronner

2020

Development

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Since its discovery 150 years ago, the neural crest has intrigued investigators owing to its remarkable developmental potential and extensive migratory ability. Cell lineage analysis has been an essential tool for exploring neural crest cell fate and migration routes. By marking progenitor cells, one can observe their subsequent locations and the cell types into which they differentiate. Here, we review major discoveries in neural crest lineage tracing from a historical perspective. We discuss how advancing technologies have refined lineage-tracing studies, and how clonal analysis can be applied to questions regarding multipotency. We also highlight how effective progenitor cell tracing, when combined with recently developed molecular and imaging tools, such as single-cell transcriptomics, single-molecule fluorescence in situ hybridization and high-resolution imaging, can extend the scope of neural crest lineage studies beyond development to regeneration and cancer initiation.

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Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells

Cited by 12 publications

References 41 publications

Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2

Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2

Pluripotent stem cell therapy for retinal diseases

Neural crest lineage analysis: from past to future trajectory

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