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SOX10 Single Transcription Factor Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

ABSTRACT: We report the use of a single transcription factor, SOX10, for the generation of oligodendrocytes from human pluripotent stem cells. We further used RNA sequencing to compare the oligodendrocytes derived from pluripotent stem cells to different primary cells. It was revealed that oligodendrocytes derived from pluripotent stem cells are representative of intermediate oligodendrocytes during embryonic development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106984 | GEO | 2017/11/17

SECONDARY ACCESSION(S): PRJNA418721

REPOSITORIES: GEO

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SOX10 Single Transcription Factor Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

Project description:SOX10 Single Transcription Factor Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

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Project description:We report a method for deriving oligodendrocyte lineage cells from human pluripotent stem cells (hPSCs) in three-dimensional (3D) culture called human oligodendrocyte spheroids (hOLS). To characterize oligodendrocyte-lineage cells in hOLS, we isolated O4+ cells by immunopanning and performed deep single cell RNA sequencing. We sequenced 295 cells and compared their profiles to unsorted cells isolated from primary human fetal cortex, primary human adult cortex, and hCS. Clustering of all cells using the t-distributed stochastic neighbor embedding (tSNE) approach revealed a distinct populations of SOX10+ oligodendrocytes, within which the O4+ cells derived from hOLS clustered most closely to oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from the primary human adult cortical tissue. Additionally, subpopulations of OPCs, newly formed oligodendrocytes, and myelinating oligodendrocytes derived were observed in the hOLS-derived cluster. To further assess the state of oligodendrocyte-lineage cells in hOLS, we performed a Monocle analysis which revealed a spectrum of oligodendrocyte-lineage stages in hOLS ranging from dividing cells that closely resembled primary OPCs to mature cells that closely resembled primary oligodendrocytes.

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Rapid and efficient generation of myelinating oligodendrocytes from human induced pluripotent stem cells using a combination of three transcription factors [hiPSC]

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SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells.

Project description:Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation.

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