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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iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF
Cecilia Laterza,Arianna Merlini,Donatella De Feo,Francesca Ruffini,Ramesh Menon,Marco Onorati,Evelien Fredrickx,Luca Muzio,Angelo Lombardo,Giancarlo Comi,Angelo Quattrini,Carla Taveggia,Cinthia Farina,Elena Cattaneo,Gianvito Martino +14 more
TL;DR: Mouse iPSC-derived NPCs-when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and further expand the therapeutic potential of NPCs derived from iPSCs in myelin disorders.
Journal ArticleDOI
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes
Matthias Pawlowski,Daniel Ortmann,Alessandro Bertero,Joana M. Tavares,Roger A. Pedersen,Ludovic Vallier,Ludovic Vallier,Mark R. N. Kotter +7 more
TL;DR: This work systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy and provides a powerful platform for the generation of human cell types by forward programming.
Journal ArticleDOI
Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
Christopher Dravis,Benjamin T. Spike,J. Chuck Harrell,Claire Johns,Christy L. Trejo,E. Michelle Southard-Smith,Charles M. Perou,Geoffrey M. Wahl +7 more
TL;DR: A signaling mechanism through which stem and mesenchymal states are acquired in mammary cells is demonstrated and therapeutic avenues in breast cancers for which targeted therapies are currently unavailable are suggested.
Journal ArticleDOI
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury
TL;DR: It is found that OPCs significantly improved locomotor performance when administered directly into the cervical spinal cord 1 week after injury, and that this functional improvement was associated with reduced parenchymal cavitation and increased sparing of myelinated axons within the injury site.
Journal ArticleDOI
Three-dimensional brain-like microenvironments facilitate the direct reprogramming of fibroblasts into therapeutic neurons
Yoonhee Jin,Jung Seung Lee,Jin Kim,Sungjin Min,Soohyun Wi,Ji Hea Yu,Gyeong Eon Chang,Ann Na Cho,Yeeun Choi,Da Hee Ahn,Sung Rae Cho,Eunji Cheong,Yun-Gon Kim,Hyong Pyo Kim,Yonghwan Kim,Dong Seok Kim,Hyun Woo Kim,Zhejiu Quan,Hoon Chul Kang,Seung Woo Cho +19 more
TL;DR: Hydrogels made from decellularized human brain tissue facilitate the direct conversion of primary mouse embryonic fibroblasts into induced neuronal cells that lead to therapeutic outcomes after transplantation in an animal model of ischaemic stroke.
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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