Generation of oligodendroglial cells by direct lineage conversion
Nan Yang,J. Bradley Zuchero,Henrik Ahlenius,Samuele Marro,Yi Han Ng,Thomas Vierbuchen,John S. Hawkins,Richard Geissler,Ben A. Barres,Marius Wernig +9 more
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 medicineread more
Citations
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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.
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Direct Lineage Reprogramming: Strategies, Mechanisms, and Applications
Jun Xu,Yuanyuan Du,Hongkui Deng +2 more
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
Ozgun Gokce,Ozgun Gokce,Geoffrey Stanley,Barbara Treutlein,Norma F. Neff,J. Gray Camp,Robert C. Malenka,Patrick E. Rothwell,Marc V. Fuccillo,Thomas C. Südhof,Thomas C. Südhof,Stephen R. Quake,Stephen R. Quake +12 more
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.
Journal ArticleDOI
Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS.
Kathrin Meyer,Laura Ferraiuolo,Carlos Henrique Miranda,Shibi Likhite,Shibi Likhite,Sohyun McElroy,Samantha R. Renusch,Dara Ditsworth,Clotilde Lagier-Tourenne,Richard A. G. Smith,John Ravits,Arthur H.M. Burghes,Pamela J. Shaw,Don W. Cleveland,Stephen J. Kolb,Brian K. Kaspar,Brian K. Kaspar +16 more
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.
References
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Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency
Takeshi Matsui,Morito Takano,Kenji Yoshida,Soichiro Ono,Chikako Fujisaki,Yumi Matsuzaki,Yoshiaki Toyama,Masaya Nakamura,Hideyuki Okano,Wado Akamatsu +9 more
TL;DR: The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.
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Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells
Fadi J. Najm,Anita Zaremba,Andrew V. Caprariello,Shreya Nayak,Eric C. Freundt,Peter C. Scacheri,Robert H. Miller,Paul J. Tesar +7 more
TL;DR: This work provides a platform for the directed differentiation of pluripotent mouse epiblast stem cells through defined developmental transitions into a pure population of highly expandable OPCs in 10 d, which robustly differentiate into myelinating oligodendrocytes in vitro and in vivo.
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Progenitor Cell–Based Treatment of the Pediatric Myelin Disorders
TL;DR: Glial progenitor cells, which can give rise to new myelinogenic oligodendrocytes, have become of great interest as potential vectors for the restoration of myelin to the dysmyelinated brain and spinal cord and may be of great utility in rectifying the Dysmyelination-associated enzymatic deficiencies of the lysosomal storage disorders.
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Stem cell treatments and multiple sclerosis.
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