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Open AccessJournal ArticleDOI

Generation of oligodendroglial cells by direct lineage conversion

TLDR
The generation of induced OPCs (iOPCs) by direct lineage conversion was reported, which gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed myelin after transplantation into shiverer mice.
Abstract
Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs More importantly, iOPCs gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed myelin after transplantation into shiverer mice We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine

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In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model.

TL;DR: It is shown that reactive glial cells in the cortex of stab-injured or Alzheimer's disease model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1.
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Cell transplantation therapy for spinal cord injury

TL;DR: A better understanding of the mechanisms whereby these cells promote functional improvements will be important to make cell transplantation a viable clinical option and may lead to the development of more targeted therapies.
Journal ArticleDOI

Direct Lineage Reprogramming: Strategies, Mechanisms, and Applications

TL;DR: Recent advances in lineage reprograming are reviewed, including the identification of novel reprogramming factors, underlying molecular mechanisms, strategies for generating functionally mature cells, and assays for characterizing induced cells.
Journal ArticleDOI

Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq

TL;DR: This work shows that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity, and identifies cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns.
References
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Supporting Online Material for Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

TL;DR: Yu et al. as discussed by the authors proposed online material for induced pluripotent stem cell lines derived from human Somatic Cells, which can be used for transplanting human stem cells to humans.
Journal ArticleDOI

A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.

TL;DR: These findings call into question the concept of a “glial” cell class as the gene profiles of astrocyte and oligodendrocytes are as dissimilar to each other as they are to neurons, for better understanding of neural development, function, and disease.
Journal ArticleDOI

Direct conversion of fibroblasts to functional neurons by defined factors

TL;DR: In this paper, a combination of three transcription factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, was used to convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro.

Invited speakers; direct conversion of fibroblasts to functional neurons by defined factors

M Wernig
TL;DR: This work identified a combination of only three factors, Ascl1, Brn2 and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro, and induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses.
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