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
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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
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
More filters
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.
Journal ArticleDOI
Cell death and control of cell survival in the oligodendrocyte lineage
B.A. Barres,I.K. Hart,H.S.R. Coles,J.F. Burne,James T. Voyvodic,William D. Richardson,Martin Raff +6 more
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.
Journal ArticleDOI
Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.
Hans S. Keirstead,Gabriel Nistor,Giovanna M. Bernal,Minodora O. Totoiu,Frank Cloutier,Kelly Sharp,Oswald Steward +6 more
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.
Journal ArticleDOI
Induction of human neuronal cells by defined transcription factors
Zhiping P. Pang,Nan Yang,Thomas Vierbuchen,Austin Ostermeier,Daniel R. Fuentes,Troy Q. Yang,Ami Citri,Vittorio Sebastiano,Samuele Marro,Thomas C. Südhof,Marius Wernig +10 more
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.
Journal ArticleDOI
Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants
Oliver Brüstle,Kimberly N. Jones,Kimberly N. Jones,Randall D. Learish,Khalad Karram,Khalid Choudhary,Khalid Choudhary,Otmar D. Wiestler,Ian D. Duncan,Ronald D.G. McKay +9 more
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.
Related Papers (5)
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
Massimiliano Caiazzo,Maria Teresa Dell’Anno,Elena Dvoretskova,Dejan Lazarevic,Dejan Lazarevic,Stefano Taverna,Damiana Leo,Tatyana D. Sotnikova,Andrea Menegon,Paola Roncaglia,Giorgia Colciago,Giovanni Russo,Piero Carninci,Gianni Pezzoli,Raul R. Gainetdinov,Stefano Gustincich,Stefano Gustincich,Alexander Dityatev,Vania Broccoli +18 more