Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA194044 | ENA |
REPOSITORIES: ENA
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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. 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.
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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: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.
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Project description: Not available
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