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

ABSTRACT: Rapid and efficient generation of myelinating oligodendrocytes from human induced pluripotent stem cells using a combination of three transcription factors

PROVIDER: PRJNA317359 | ENA |

REPOSITORIES: ENA

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

Project description:We demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in hiPSC-derived neural progenitor cells (hiPSC-NPC) is sufficient to rapidly generate O4+ oligodendrocytes with an efficiency of 60 to 70% within 28 days.

2017-03-06 | GSE79913 | GEO

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

2017-03-06 | GSE79912 | GEO

Induction of Myelinating Oligodendrocytes in Human Cortical Spheroids

Project description:Induction of Myelinating Oligodendrocytes in Human Cortical Spheroids

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RNA-seq of myelinating oligodendrocytes in Lmna wt and knockout mice

Project description:We showed that the composition of the nucler lamina changes with the differentiation state of oligodendrocyte lineage cells, with Lamin B highly expressed in progenitor cells and Lamin A highly expressed in mature oligodendrocytes. The genetic deletion of Lmna in oligodendrocytes results in the onset of a progressive motor phenotype in adult mice. We performed RNA-Seq in myelinating oligodendrocytes expressing the reporter myelin marker NDRG1-EGFP ( Marechal et al., 2021) in the presence or absence of LMNA. The goal is to identify the transcriptome profile in mice LMNA ablated cells compared to the controls.

2023-06-21 | GSE222574 | GEO

Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids.

Project description:Human stem cell derived brain organoids are increasingly gaining attention as an ideal model system for investigating neurological diseases, particularly those that involve myelination defects. However, current protocols for generating brain organoids with sufficiently mature oligodendrocytes that deposit myelin on endogenously produced neurons are lengthy and complicated. Taking advantage of a human pluripotent stem cell line that reports on SOX10 expression, we developed a protocol that involves a 42 day exposure of neuroectoderm-derived organoids to a cocktail of growth factors and small molecules that collectively foster oligodendrocyte specification and survival. Importantly, the resulting day 42 brain organoids contain both myelinating oligodendrocytes, cortical neuronal cells and astrocytes. These oligodendrocyte brain organoids therefore constitute a valuable and tractable platform for functional neurogenomics and drug screening for white matter diseases.

| S-EPMC8010307 | biostudies-literature

ATAC-seq in myelinating oligodendrocytes from wt and Lmna knockout mice

Project description:We showed that the composition of the nuclear lamina changes with the differentiation state of oligodendrocyte lineage cells, with Lamin B highly expressed in progenitor cells and Lamin A highly expressed in mature oligodendrocytes. The genetic deletion of LMNA in mice results in the onset of a progressive motor phenotype in adult mice. We performed ATAC-Seq in myelinating Oligodendrocytes expressing the myelin marker NDRG1-EGFP ( Marechal et al., 2021) in the presence or absence of LMNA. The goal is to identify regions of chromatin accessibility that distinguish the LMNA KO mutant cells from the WT.

2023-06-01 | GSE190404 | GEO

Induction of Myelinating Oligodendrocytes in Human Cortical Spheroids

Project description:Organoid technologies provide an accessible system in which to examine the generation, self-organization,and 3-dimensional cellular interactions during development of the human cerebral cortex. However, oligodendrocytes, the myelinating glia of the central nervous system and third major neural cell type, are conspicuously absent from current protocols. Here we reproducibly generate human oligodendrocytes and myelin in pluripotent stem cell-derived cortical spheroids. Transcriptional and immunohistochemical analysis of the spheroids demonstrates molecular features consistent with maturing human oligodendrocytes within 14 weeks of culture, including expression of MyRF, PLP1, and MBP proteins. Histological analysis by electron microscopy shows initial wrapping of human neuronal axons with myelin by 20 weeks and maturation to compact myelin by 30 weeks in culture. Treatment of spheroids with previously identified promyelinating drugs enhances the rate and extent of human oligodendrocyte generation and myelination. Furthermore, generation of spheroids from patients with a severe genetic myelin disorder, Pelizaeus-Merzbacher disease, demonstrates the ability to recapitulate human disease phenotypes, which were in turn improved with both pharmacologic and CRISPR-based approaches. Collectively, these 3-dimensional, multi-lineage cortical spheroids provide a versatile platform to observe and perturb the complex cellular interactions that occur during developmental myelination of the brain and offer new opportunities for disease modeling and therapeutic development in human tissue.

2018-07-30 | GSE110006 | GEO

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

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

2017-03-06 | GSE79914 | GEO

Transcription profiling of rat perineuronal A2B5/OTMP+ oligodendrocytes

Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for â we speculate â a pathological eventuality. We posit that the signature molecules PDGFR-Î±Î², cytokine PDGF-CC, and the transcription factor Pea3 used â among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Experiment Overall Design: Flow Cytometry was used to isolate A2B5/OTMP+ oligodendrocytes from postnatal day 7 rat brain. 4 bioloical replicates were obtained. This data can be compared to the previously submitted oligodendrocyte expression data (GSE5940).

2008-06-18 | E-GEOD-11277 | biostudies-arrayexpress

A2B5/OTMP+ rat perineuronal oligodendrocytes

Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for – we speculate – a pathological eventuality. We posit that the signature molecules PDGFR-αβ, cytokine PDGF-CC, and the transcription factor Pea3 used – among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Keywords: developmental

2008-06-01 | GSE11277 | GEO

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