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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.
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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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Journal ArticleDOI

Remyelination in the CNS: from biology to therapy

TL;DR: The mechanisms of remyelination provide critical clues for regeneration biologists that help them to determine why remYelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.
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Cell death and control of cell survival in the oligodendrocyte lineage

TL;DR: It is shown that about 50% of oligodendrocytes normally die in the developing rat optic nerve, apparently as a result of a competition for limiting amounts of survival signals and that a requirement for survival signals is more general than previously thought.
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Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

TL;DR: It is shown that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function.
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Induction of human neuronal cells by defined transcription factors

TL;DR: The data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors.
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Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants

TL;DR: Transplantation in a rat model of a human myelin disease shows that ES cell-derived precursors interact with host neurons and efficiently myelinate axons in brain and spinal cord.
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