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Journal ArticleDOI

Generation of oligodendroglial cells by direct lineage conversion

01 May 2013-Nature Biotechnology (Nature Research)-Vol. 31, Iss: 5, pp 434-439
TL;DR: 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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Citations
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Journal ArticleDOI
Ziyuan Guo1, Lei Zhang1, Zheng Wu1, Yuchen Chen1, Fan Wang1, Gong Chen1 
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.

630 citations


Additional excerpts

  • ..., 2011) or oligodendroglial cells (Najm et al., 2013; Yang et al., 2013)....

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  • ...…2011; Kim et al., 2011; Ladewig et al., 2012; Liu et al., 2012, 2013; Meng et al., 2012; Pang et al., 2011; Pfisterer et al., 2011; Qiang et al., 2011; Son et al., 2011; Torper et al., 2013; Vierbuchen et al., 2010; Yoo et al., 2011) or oligodendroglial cells (Najm et al., 2013; Yang et al., 2013)....

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Journal ArticleDOI
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.
Abstract: Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction. Currently, there is no effective treatment for the injured spinal cord. The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord injury. However, little is known about the mechanisms through which these individual cell types promote repair and functional improvements. The five most commonly proposed mechanisms include neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration. A better understanding of the mechanisms whereby these cells promote functional improvements, as well as an appreciation of the obstacles in implementing these therapies and effectively modeling spinal cord injury, will be important to make cell transplantation a viable clinical option and may lead to the development of more targeted therapies.

529 citations

Journal ArticleDOI
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.

344 citations

Journal ArticleDOI
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.

334 citations


Cites background from "Generation of oligodendroglial cell..."

  • ...Among them are Sox9 for astrocytes (Caiazzo et al., 2015), Sox10 for oligodendrocytes (Yang et al., 2013), Gata2 for endothelial cells (Elcheva et al., 2014), and Maf for macrophages (Hegde et al., P cb p4 R bf ox 2 S nr pn C el f5 C el f4 R bf o x 1 C el f2 C el f1 Tx nl 4a E l a vl 3 P si p1 C el…...

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  • ...The most cell type-specific TFs we found were often previously observed to fuel direct conversion of cells into that cell type (Caiazzo et al., 2015; Elcheva et al., 2014; Hegde et al., 1999; Pang et al., 2011; Vierbuchen et al., 2010; Yang et al., 2013)....

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Journal ArticleDOI
TL;DR: Easy production and expansion of i-astrocytes now enables rapid disease modeling and high-throughput drug screening to alleviate astrocyte-derived toxicity, suggesting a common mechanism of ALS.
Abstract: Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration, paralysis, and death. Accurate disease modeling, identifying disease mechanisms, and developing therapeutics is urgently needed. We previously reported motor neuron toxicity through postmortem ALS spinal cord-derived astrocytes. However, these cells can only be harvested after death, and their expansion is limited. We now report a rapid, highly reproducible method to convert adult human fibroblasts from living ALS patients to induced neuronal progenitor cells and subsequent differentiation into astrocytes (i-astrocytes). Non-cell autonomous toxicity to motor neurons is found following coculture of i-astrocytes from familial ALS patients with mutation in superoxide dismutase or hexanucleotide expansion in C9orf72 (ORF 72 on chromosome 9) the two most frequent causes of ALS. Remarkably, i-astrocytes from sporadic ALS patients are as toxic as those with causative mutations, suggesting a common mechanism. Easy production and expansion of i-astrocytes now enables rapid disease modeling and high-throughput drug screening to alleviate astrocyte-derived toxicity.

302 citations

References
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Journal ArticleDOI
25 Aug 2006-Cell
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.

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Journal ArticleDOI
30 Nov 2007-Cell
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.

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Journal ArticleDOI
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
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16,371 citations

Journal ArticleDOI
21 Dec 2007-Science
TL;DR: This article showed that OCT4, SOX2, NANOG, and LIN28 factors are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.
Abstract: Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.

9,836 citations

Journal ArticleDOI
TL;DR: This work generated induced pluripotent stem cells capable of germline transmission from murine somatic cells by transd, and demonstrated the ability of these cells to reprogram into patient-specific and disease-specific stem cells.
Abstract: If it were possible to reprogram differentiated human somatic cells into a pluripotent state, patient-specific and disease-specific stem cells could be developed. Previous work generated induced pluripotent stem (iPS) cells capable of germline transmission from murine somatic cells by transd

4,034 citations