RNA-seq of in vitro reprogrammed mouse pericytes to oligodendrocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Charles Girardot
PROVIDER: E-MTAB-8453 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Direct conversion of pericytes (PCs) into induced oligodendrocytes (iOPCs) by ectopic expression of Olig2 and Sox10 (2F) was assessed by chromatin accessibility profiling (by ATAC-seq). Samples were collected before and after direct conversion (at 3 different time points/passages - p5, p15 and p25).
2021-03-07 | E-MTAB-8452 | biostudies-arrayexpress
Project description:Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to ‘induced’ oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies. 6 total samples were analyzed. MEFs were either untreated or infected with inducible lentiviral vectors containing the open reading frames of transcription factors. Samples were compared to bona fide OPCs.
2013-04-14 | E-GEOD-45440 | biostudies-arrayexpress
Project description:We report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to convert mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures that resemble OPCs. We compared the global gene expression pattern of iOPCs, fibroblasts, primary OPCs from the neonatal rat brain, and their differentiated progeny. We purified iOPCs by O4 immunopanning three weeks after infection and extracted total RNA. Acutely isolated rat cortical OPCs were either used directly for RNA extraction or expanded in mitogen-containing media for 24h before switching into differentiation medium, lacking PDGF/NT-3 and containing T3. Cells were harvested for microarray analysis 3 and 6 days after induction of differentiation.
2013-04-07 | E-GEOD-40421 | biostudies-arrayexpress
Project description:Many studies have already shown the reprogramming of somatic cells into other cell types such as neural stem cells, blood progenitor cells, and hepatocytes by inducing combinations of transcription factors. One of the recent development in cellular reprogramming is the direct reprogramming, that can change cell fate towards different lineages. This strategy provides an alternative to the use of pluripotent stem cells ruling out the concerns of tumorigenicity caused by undifferentiated cell populations. Here, we generated induced oligodendrocyte progenitor cells (iOPCs) from mouse fibroblasts by direct reprogramming. The generated iOPCs are homogenous, self-renewing, and multipotent. Once differentiated, the somatic stem cells exhibit morphological and molecular characteristics of oligodendrocyte progenitor cells (OPCs). Thus, we demonstrated that terminally differentiated somatic cells can be converted into functional iOPCs by induction of transcription factors offering a new strategies to cure myelin disorders. To identify the global gene expression profiles of iOPCs, we analyzed total 6 samples.
2015-11-02 | E-GEOD-52035 | biostudies-arrayexpress
Project description:Mesenchymal stromal cells (MSCs) are cultured cells that can give rise to mature mesenchymal cells under appropriate conditions, and secrete a number of biologically relevant molecules that may play an important role in regenerative medicine. Evidence indicates that pericytes (PCs) correspond to mesenchymal stem cells in vivo and can give rise to MSCs when cultured, but a comparison between the gene expression profiles of cultured PCs (cPCs) and MSCs is lacking. We have devised a novel methodology to isolate PCs from human adipose tissue, and compared cPCs to MSCs obtained through traditional methods. Freshly isolated PCs expressed CD34, CD140b, and CD271 on their surface, but not CD146. Both MSCs and cPCs were able to differentiate along mesenchymal pathways in vitro, displayed an essentially identical surface immunophenotype, and exhibited the ability to suppress CD3+ lymphocyte proliferation in vitro. Microarray expression data of cPCs and MSCs formed a single cluster among other cell types. Further analyses showed that the gene expression profiles of cPCs and MSCs are extremely similar, although MSCs differentially expressed endothelial cell-specific transcripts. These results confirm, using the power of transcriptomic analysis, that PCs give rise to MSCs, and suggest that low levels of endothelial cells may persist in MSC cultures established using traditional protocols. Highly purified human adipose-tissue pericytes (AT3G5Cs) were isolated based on the expression of the antigen detected by the 3G5 antibody, lack of expression of CD31, and ability to adhere to tissue-cultured plastic whithin a short time. The in vitro properties of cultured AT3G5Cs were compared to those of adipose tissue mesenchymal stromal cells (ATMSCs) obtained through traditional methods. Gene expression profiles of cultured AT3G5Cs (n = 3 different biological samples) and ATMSCs (n = 3 different biological samples) were compared to each other by statistical analyses. Gene expression profiles of cultured AT3G5Cs and ATMSCs were compared to those of other cell types by clustering analyses.
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Project description:We report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to convert mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures that resemble OPCs.
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Project description:Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR-? signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-?. Inactivation of the PDGFR-? signaling system led to decreased levels of integrin ?1?1, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis. Pericytes were isolated and treated with PDGF-BB or control for 5 days.
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Project description:Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to ‘induced’ oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.
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Project description:Mouse 129-B13 ESCs were genetically modified using CRISPR-Cas9 with two guides to remove exon 4 of Rai1, single-cell sorted and expanded to establish modified cell lines. Additionally, cell lines derived from unsuccessfully modified lines were used as "wild-type" controls. 3 lines of each group were used as biological replicates. Samples were differentiated from mouse ESCs (Day 0) to neural progenitor cells (Day 8) and glutamatergic neurons (Day 12). NEBNext Poly(A) mRNA Magnetic Isolation Module was used to enrich mRNA. Nonsense-mediated decay was not observed in Rai1 ex 4 KOs.
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