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Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161417 | GEO | 2023/03/26

REPOSITORIES: GEO

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Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [bulk_RNAseq]

Project description:Inherited retinal diseases and aged related macular degeneration are main causes of blindness that involves irreversible photoreceptor loss. Gene therapy approaches do not prevent photoreceptor degeneration during disease progression, and to date protocols for generating photoreceptors from pluripotent stem cells do not exist. Therefore, transplantation of photoreceptors containing retinal organoids is considered a potential option. However, in vitro formation of organoids requires animal-derived materials and they vary considerably in cell composition between batches, which strongly limits their applications in therapy. Here, we show that human recombinant retina-specific laminin isoform LN523, normally present in the extra cellular matrix ECM surrounding photoreceptors, supports differentiation of pluripotent embryonic stem cells to photoreceptor progenitors in vitro. Using a rabbit macular degeneration model, the transplanted and engrafted cells mature in vivo and form synaptic connectivity with the host retina. Furthermore, addition of a rod-derived cone viability factor increased the formation of cone photoreceptors. These results may pave the way for cell therapy treatment of macular degeneration.

2023-03-26 | GSE161414 | GEO

Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [single cell_RNAseq]

2023-03-26 | GSE161416 | GEO

Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors

Project description:Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors

| PRJNA678242 | ENA

Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [bulk_RNAseq]

Project description:Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [bulk_RNAseq]

| PRJNA678241 | ENA

Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [single cell_RNAseq]

Project description:Retina-Specific Laminin 523 Drives Differentiation of Human Pluripotent Stem Cells to Photoreceptors [single cell_RNAseq]

| PRJNA678246 | ENA

Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina.

Project description:Absence of a regenerative pathway for damaged retina following injury or disease has led to experiments using stem cell transplantation for retinal repair, and encouraging results have been obtained in rodents. The swine eye is a closer anatomical and physiological match to the human eye, but embryonic stem cells have not been isolated from pig, and photoreceptor differentiation has not been demonstrated with induced pluripotent stem cells (iPSCs) of swine. Here, we subjected iPSCs of swine to a rod photoreceptor differentiation protocol consisting of floating culture as embryoid bodies followed by differentiation in adherent culture. Real-time PCR and immunostaining of differentiated cells demonstrated loss of expression of the pluripotent genes POU5F1, NANOG, and SOX2 and induction of rod photoreceptor genes RCVRN, NRL, RHO, and ROM1. While these differentiated cells displayed neuronal morphology, culturing on a Matrigel substratum triggered a further morphological change resulting in concentration of rhodopsin (RHO) and rod outer segment-specific membrane protein 1 in outer segment-like projections resembling those on primary cultures of rod photoreceptors. The differentiated cells were transplanted into the subretinal space of pigs treated with iodoacetic acid to eliminate rod photoreceptors. Three weeks after transplantation, engrafted RHO+ cells were evident in the outer nuclear layer where photoreceptors normally reside. A portion of these transplanted cells had generated projections resembling outer segments. These results demonstrate that iPSCs of swine can differentiate into photoreceptors in culture, and these cells can integrate into the damaged swine neural retina, thus, laying a foundation for future studies using the pig as a model for retinal stem cell transplantation.

| S-EPMC4263955 | biostudies-literature

Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-11-08 | GSE85784 | GEO

Somatostatin signalling promotes the differentiation of rod photoreceptors in human pluripotent stem cell-derived retinal organoid.

Project description:ObjectivesStem cell-derived photoreceptor replacement therapy is a promising strategy for the treatment of retinal degenerative disease. The development of 3D retinal organoids has permitted the production of photoreceptors. However, there is no strategy to enrich a specific photoreceptor subtype due to inadequate knowledge of the molecular mechanism underlying the photoreceptor fate determination. Hence, our aim is to explore the uncharacterized function of somatostatin signalling in human pluripotent stem cell-derived photoreceptor differentiation.Materials and methods3D retinal organoids were achieved from human embryonic stem cell. The published single-cell RNA-sequencing datasets of human retinal development were utilized to further investigate the transcriptional regulation of photoreceptor differentiation. The assays of immunofluorescence staining, lentivirus transfection, real-time quantitative polymerase chain reaction and western blotting were performed.ResultsWe identified that the somatostatin receptor 2 (SSTR2)-mediated signalling was essential for rod photoreceptor differentiation at the precursor stage. The addition of the cognate ligand somatostatin in human 3D retinal organoids promoted rod photoreceptor differentiation and inhibited cone photoreceptor production. Furthermore, we found that the genesis of rod photoreceptors was modulated by endogenous somatostatin specifically secreted by developing retinal ganglion cells.ConclusionsOur study identified SSTR2 signalling as a novel extrinsic regulator for rod photoreceptor fate determination in photoreceptor precursors, which expands the repertoire of functional signalling pathways in photoreceptor development and sheds light on the optimization of the photoreceptor enrichment strategy.

| S-EPMC9251046 | biostudies-literature

Inducible MLL-AF9 Expression Drives an AML Program during Human Pluripotent Stem Cell-Derived Hematopoietic Differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-03 | GSE217015 | GEO

Pluripotent mouse Embryonic Stem Cells and during Retinoic Acid-induced differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-05-01 | E-GEOD-65698 | biostudies-arrayexpress