Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells
Fadi J. Najm,Angela M. Lager,Anita Zaremba,Krysta Wyatt,Andrew V. Caprariello,Daniel C. Factor,Robert T. Karl,Tadao Maeda,Robert H. Miller,Paul J. Tesar +9 more
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TLDR
Direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors shows a bipolar morphology and global gene expression profile consistent with bona fide OPCs.Abstract:
Two studies show direct conversion of mouse embryonic fibroblasts to oligodendrocyte progenitor cells capable of generating myelinating oligodendrocytes.read more
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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.
Journal ArticleDOI
Neural Stem Cells: Generating and Regenerating the Brain
Fred H. Gage,Sally Temple +1 more
TL;DR: Together with reprogramming technology, human somatic cell-derived NSCs and their progeny can model neurological diseases with improved accuracy and anticipate further important discoveries and novel therapies based on the knowledge and application of these powerful cells.
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
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.
Fadi J. Najm,Mayur Madhavan,Anita Zaremba,Elizabeth Shick,Robert T. Karl,Daniel C. Factor,Tyler E. Miller,Tyler E. Miller,Zachary S. Nevin,Christopher Kantor,Alex Sargent,Kevin L. Quick,Daniela Schlatzer,Hong Tang,Ruben Papoian,Kyle R. Brimacombe,Min Shen,Matthew B. Boxer,Ajit Jadhav,Andrew P. Robinson,Joseph R. Podojil,Stephen D. Miller,Robert H. Miller,Robert H. Miller,Paul J. Tesar +24 more
TL;DR: Seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes from progenitor cells in vitro and provide a rationale for testing miconazole and clobetasol, or structurally modified derivatives, to enhance remyelination in patients.
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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GREAT improves functional interpretation of cis-regulatory regions
Cory Y. McLean,Dave Bristor,Michael Hiller,Shoa L. Clarke,Bruce T. Schaar,Craig B. Lowe,Aaron M. Wenger,Gill Bejerano +7 more
TL;DR: The Genomic Regions Enrichment of Annotations Tool (GREAT) is developed to analyze the functional significance of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome.
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.
Journal ArticleDOI
Serial block−face scanning electron microscopy to reconstruct three−dimensional tissue nanostructure
Winfried Denk,Heinz Horstmann +1 more
TL;DR: It is demonstrated that datasets meeting these requirements can be obtained by automated block-face imaging combined with serial sectioning inside the chamber of a scanning electron microscope, opening the possibility of automatically obtaining the electron-microscope-level 3D datasets needed to completely reconstruct the connectivity of neuronal circuits.
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