Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq, ATAC-seq and DNA-methylation array data of human oligodendrocyte-like cells derived from transdifferentiated fibroblasts

ABSTRACT: One-step reprogramming of human fibroblasts into oligodendrocyte-like cells. We characterized the expression, chromatin accessibility and methylation profile of human oligodendrocyte-like cells derived using a new protocol for the direct transdifferentiation of human fibroblasts into oligodendrocyte-like cells. Direct conversion of fibroblasts was induced by ectopic overexpression of SOX10, OLIG2 and NKX6.2. The aim of the experiments was to characterise the transcriptional response and associated chromatin changes following transdifferentiation. In addition, profiles of primary human oligodendrocytes were produced.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Benjamín Hernández-Rodríguez

PROVIDER: E-MTAB-7838 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2.

Chanoumidou Konstantina K Hernández-Rodríguez Benjamín B Windener Farina F Thomas Christian C Stehling Martin M Mozafari Sabah S Albrecht Stefanie S Ottoboni Linda L Antel Jack J Kim Kee-Pyo KP Velychko Sergiy S Cui Qiao Ling QL Xu Yu Kang T YKT Martino Gianvito G Winkler Jürgen J Schöler Hans R HR Baron-Van Evercooren Anne A Boespflug-Tanguy Odile O Vaquerizas Juan M JM Ehrlich Marc M Kuhlmann Tanja T

Stem cell reports 20210325 4

Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6.2 in human fibroblasts results in rapid generation of O4<sup>+</sup> cells, which further differentiate into MBP<sup>+</sup> mature oli ...[more]

PMID: 33770499

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Project description:In vitro neural stem cell models are widely used to model a wide range of neuropsychiatric conditions. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease. In this GEO submission, we upload data from 5 lines of phNPCs as well as hiPSCs cultured in two different laboratories all at multiple differentiation time points. phNPCs: For each of 5 lines generated from 3 donors (15-16 PCW), two independent differentiation experiments each containing two replicates were performed and harvested at four time points (1, 4, 8, 12 wks PD; ~16 samples per line; 77 total samples). We confirmed RNA integrity by RIN score with the Agilent 2100 Bioanalyzer (mean +/- sd: 9.16 +/- 0.78). iPSC: Two hiPSC datasets were RNA profiled as part of this study. hiPSCs grown in the Kosik lab was derived from two independent, non-isogenic IPS lines: one derived from a patient carrying a mutant Tau variant G55R and one reference control. For each of these lines, two samples were harvested at each of 0, 1, 4, and 8 weeks PD (total n=16 samples). hiPSCs grown in the Gage lab were from six samples derived from 3 control lines at each of two time points (0 and 4 wk PD, total n=12 samples). Samples were randomized to microarray chip by all biological variables of interest (donor, line, passage, replicate number, differentiation week, plate date, and RIN) to control for potential batch effects.

Dataset Information

RNA-seq, ATAC-seq and DNA-methylation array data of human oligodendrocyte-like cells derived from transdifferentiated fibroblasts

Publications

One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2.

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