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
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Direct Conversion of Fibroblasts into Functional Astrocytes by Defined Transcription Factors
Massimiliano Caiazzo,Serena Giannelli,Pierluigi Valente,Gabriele Lignani,Annamaria Carissimo,Alessandro Sessa,Gaia Colasante,Rosa Bartolomeo,Luca Massimino,Stefano Ferroni,Carmine Settembre,Fabio Benfenati,Fabio Benfenati,Vania Broccoli +13 more
TL;DR: Direct cell reprogramming enables direct conversion of fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell-lineage-specific transcription factors and it is proved both by gene-expression profiling and functional tests that iAstrocytes are comparable to native brain astroCytes.
Journal ArticleDOI
How to make an oligodendrocyte.
TL;DR: The molecular events regulating oligodendrocyte development in vivo are described and approaches to generate oligodENDrocytes in vitro are discussed, which include approaches to modulate their differentiation and myelinogenesis in vivo following transplantation.
Journal ArticleDOI
Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking
TL;DR: This Perspective seeks to define those neurological conditions most appropriate for cell replacement therapy by considering its potential efficacy and clinical feasibility in those disorders, as well as potential impediments to its application.
Journal ArticleDOI
Glia Disease and Repair—Remyelination
TL;DR: The biology of remyelination is reviewed, including the cells and signals involved; when remyElination occurs and when and why it fails and the consequences of its failure are described; approaches for therapeutically enhancing remyELination in demyelinating diseases of both children and adults are discussed.
Journal ArticleDOI
In Vivo Reprogramming of Striatal NG2 Glia into Functional Neurons that Integrate into Local Host Circuitry
Olof Torper,Daniella Rylander Ottosson,Maria Pereira,Shong Lau,Tiago Cardoso,Shane Grealish,Malin Parmar +6 more
TL;DR: An adeno-associated virus-based reporter system that allows selective GFP labeling of reprogrammed neurons is developed that allows mapping of 3D circuitry integration into local and distal brain regions and shows that the newly reprogramed neurons are integrated into host brain.
References
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Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
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.
Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
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.
Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
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.
Journal ArticleDOI
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 Stewart,Igor I. Slukvin,James A. Thomson +11 more
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.
Journal ArticleDOI
Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
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.
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