Dataset Information

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

ABSTRACT: Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.

SUBMITTER: Liu YV

PROVIDER: S-EPMC10202694 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Liu Ying V YV Santiago Clayton P CP Sogunro Akin A Konar Gregory J GJ Hu Ming-Wen MW McNally Minda M MM Lu Yu-Chen YC Flores-Bellver Miguel M Aparicio-Domingo Silvia S Li Kang V KV Li Zhuo-Lin ZL Agakishiev Dzhalal D Hadyniak Sarah E SE Hussey Katarzyna A KA Creamer Tyler J TJ Orzolek Linda D LD Teng Derek D Canto-Soler M Valeria MV Qian Jiang J Jiang Zheng Z Johnston Robert J RJ Blackshaw Seth S Singh Mandeep S MS

Stem cell reports 20230501 5

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal ...[more]

PMID: 37163980

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Project description:Little is known about the molecular pathogenesis of schizophrenia, possibly because of unrecognized heterogeneity in diagnosed patient populations. We analyzed gene expression data collected from the dorsolateral prefrontal cortex (DLPFC) of post-mortem frozen brains of 189 adult diagnosed schizophrenics and 206 matched controls. Transcripts from 633 genes are differentially expressed in the DLPFC of schizophrenics as compared to controls at Bonferroni-corrected significance levels. Seventeen of those genes are differentially expressed at very high significance levels (<10-8 after Bonferroni correction). The findings were closely replicated in a dataset from an entirely unrelated source. The statistical significance of this differential gene expression is being driven by about half of the schizophrenic DLPFC samples, and importantly, it is the same half of the samples that is driving the significance for almost all of the differentially expressed transcripts. Weighted gene co-expression network analysis (WGCNA) of the schizophrenic subjects, based on the transcripts differentially expressed in the schizophrenics as compared to controls, divides them into two groups. "Type 1" schizophrenics have a DLPFC transcriptome similar to that of controls with only four differentially expressed genes identified. "Type 2" schizophrenics have a DLPFC transcriptome dramatically different from that of controls, with 3529 expression array probes to 3092 genes detecting transcripts that are differentially expressed at very high significance levels. These findings were re-tested and replicated in a separate independent cohort, using the RNAseq data from the DLPFC of an independent set of schizophrenics and control subjects. We suggest the hypothesis that these striking differences in DLPFC transcriptomes, identified and replicated in two populations, imply a fundamental biologic difference between these two groups of diagnosed schizophrenics, and we propose specific paths for further testing and expanding the hypothesis.

Dataset Information

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Publications

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Similar Datasets

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