» Articles » PMID: 23584611

Transcription Factor-mediated Reprogramming of Fibroblasts to Expandable, Myelinogenic Oligodendrocyte Progenitor Cells

Overview
Journal Nat Biotechnol
Specialty Biotechnology
Date 2013 Apr 16
PMID 23584611
Citations 142
Authors
Affiliations
Soon will be listed here.
Abstract

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 morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. 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.

Citing Articles

Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.

Gao Y, Slomnicki L, Kilanczyk E, Forston M, Pietrzak M, Rouchka E ASN Neuro. 2024; 16(1):2371162.

PMID: 39024571 PMC: 11262469. DOI: 10.1080/17590914.2024.2371162.


Lineage Reprogramming: Genetic, Chemical, and Physical Cues for Cell Fate Conversion with a Focus on Neuronal Direct Reprogramming and Pluripotency Reprogramming.

Umeyama T, Matsuda T, Nakashima K Cells. 2024; 13(8.

PMID: 38667322 PMC: 11049106. DOI: 10.3390/cells13080707.


Conversion of Astrocyte Cell Lines to Oligodendrocyte Progenitor Cells Using Small Molecules and Transplantation to Animal Model of Multiple Sclerosis.

Sharifi-Kelishadi M, Zare L, Fathollahi Y, Javan M J Mol Neurosci. 2024; 74(2):40.

PMID: 38594388 DOI: 10.1007/s12031-024-02206-6.


Pervasive environmental chemicals impair oligodendrocyte development.

Cohn E, Clayton B, Madhavan M, Lee K, Yacoub S, Fedorov Y Nat Neurosci. 2024; 27(5):836-845.

PMID: 38528201 PMC: 11088982. DOI: 10.1038/s41593-024-01599-2.


Glial-restricted progenitor cells: a cure for diseased brain?.

Rogujski P, Lukomska B, Janowski M, Stanaszek L Biol Res. 2024; 57(1):8.

PMID: 38475854 PMC: 10935984. DOI: 10.1186/s40659-024-00486-1.


References
1.
Bogler O, Wren D, Barnett S, Land H, Noble M . Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Proc Natl Acad Sci U S A. 1990; 87(16):6368-72. PMC: 54535. DOI: 10.1073/pnas.87.16.6368. View

2.
Beard C, Hochedlinger K, Plath K, Wutz A, Jaenisch R . Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells. Genesis. 2006; 44(1):23-8. DOI: 10.1002/gene.20180. View

3.
Sim F, McClain C, Schanz S, Protack T, Windrem M, Goldman S . CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol. 2011; 29(10):934-41. PMC: 3365580. DOI: 10.1038/nbt.1972. View

4.
Barres B, Lazar M, Raff M . A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development. 1994; 120(5):1097-108. DOI: 10.1242/dev.120.5.1097. View

5.
Rowitch D, Kriegstein A . Developmental genetics of vertebrate glial-cell specification. Nature. 2010; 468(7321):214-22. DOI: 10.1038/nature09611. View