Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes
Summary: The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs...
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doaj-594d5418d1c949c7875666a1d7d874ca2020-11-25T00:12:09ZengElsevierStem Cell Reports2213-67112017-04-0184803812Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and OligodendrocytesMatthias Pawlowski0Daniel Ortmann1Alessandro Bertero2Joana M. Tavares3Roger A. Pedersen4Ludovic Vallier5Mark R.N. Kotter6Anne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding authorAnne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UKAnne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0QQ, UKAnne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UKAnne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKAnne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0QQ, UK; Corresponding authorSummary: The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes. : In this article, Pawlowski and colleagues report a dual genomic safe harbor targeting approach for optimized inducible transgene expression in human pluripotent stem cells (hPSCs). The optimized inducible expression of reprogramming factors in hPSCs enables deterministic forward programming into mature cell types. This is exemplified by the rapid, single-step generation of neurons, skeletal myocytes, and oligodendrocytes. Keywords: human pluripotent stem cells, reprogramming, skeletal myocytes, oligodendrocyte progenitor cells, neuronshttp://www.sciencedirect.com/science/article/pii/S2213671117300838 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthias Pawlowski Daniel Ortmann Alessandro Bertero Joana M. Tavares Roger A. Pedersen Ludovic Vallier Mark R.N. Kotter |
spellingShingle |
Matthias Pawlowski Daniel Ortmann Alessandro Bertero Joana M. Tavares Roger A. Pedersen Ludovic Vallier Mark R.N. Kotter Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes Stem Cell Reports |
author_facet |
Matthias Pawlowski Daniel Ortmann Alessandro Bertero Joana M. Tavares Roger A. Pedersen Ludovic Vallier Mark R.N. Kotter |
author_sort |
Matthias Pawlowski |
title |
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes |
title_short |
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes |
title_full |
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes |
title_fullStr |
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes |
title_full_unstemmed |
Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes |
title_sort |
inducible and deterministic forward programming of human pluripotent stem cells into neurons, skeletal myocytes, and oligodendrocytes |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2017-04-01 |
description |
Summary: The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes. : In this article, Pawlowski and colleagues report a dual genomic safe harbor targeting approach for optimized inducible transgene expression in human pluripotent stem cells (hPSCs). The optimized inducible expression of reprogramming factors in hPSCs enables deterministic forward programming into mature cell types. This is exemplified by the rapid, single-step generation of neurons, skeletal myocytes, and oligodendrocytes. Keywords: human pluripotent stem cells, reprogramming, skeletal myocytes, oligodendrocyte progenitor cells, neurons |
url |
http://www.sciencedirect.com/science/article/pii/S2213671117300838 |
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