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
Supporting Online Material for Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Junying Yu,Maxim A. Vodyanik,Kim Smuga-Otto,Jessica Antosiewicz-Bourget,Jennifer L. Frane,Shulan Tian,Jeff Nie,Gudrun A. Jonsdottir,Victor Ruotti,Ron M. Stewart,Igor I. Slukvin,James A. Thomson +11 more
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
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Journal ArticleDOI
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
John D. Cahoy,Ben Emery,Amit Kaushal,Lynette C. Foo,Jennifer L. Zamanian,Karen S. Christopherson,Yi Xing,Jane L. Lubischer,Paul A. Krieg,Sergey A. Krupenko,Wesley J. Thompson,Ben A. Barres +11 more
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
Thomas Vierbuchen,Austin Ostermeier,Zhiping P. Pang,Yuko Kokubu,Thomas C. Südhof,Marius Wernig +5 more
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
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.
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