Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State

Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)...

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Bibliographic Details
Published in:Cell stem cell Vol. 21; no. 2; p. 264
Main Authors: Li, Xiang, Liu, Defang, Ma, Yantao, Du, Xiaomin, Jing, Junzhan, Wang, Lipeng, Xie, Bingqing, Sun, Da, Sun, Shaoqiang, Jin, Xueqin, Zhang, Xu, Zhao, Ting, Guan, Jingyang, Yi, Zexuan, Lai, Weifeng, Zheng, Ping, Huang, Zhuo, Chang, Yanzhong, Chai, Zhen, Xu, Jun, Deng, Hongkui
Format: Journal Article
Language:English
Published: United States 03.08.2017
Subjects:
Aging
Animals
Animals, Newborn
Brain - cytology
Cell Differentiation
Cell Lineage
Cell Survival
Cells, Cultured
Cellular Reprogramming
Endoderm - cytology
Extraembryonic Membranes - cytology
Female
Fibroblasts - metabolism
Gene Expression Profiling
Genomic Instability
Green Fluorescent Proteins - metabolism
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Male
Mice
Neurons - cytology
Neurons - metabolism
Neurons - transplantation
Transcription, Genetic
long-term expansion
chemical reprogramming
chemically-induced XEN-like state
functional neurons
direct reprogramming
multifunctional XEN-like state
functional hepatocyte
lineage reprogramming
expandable XEN-like state
neural reprogramming
ISSN:1875-9777, 1875-9777
Online Access:Get more information
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Summary:Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain. Using similar principles, we were also able to induce hepatocyte-like cells from the XEN-like cells. Cells in the induced XEN-like state were readily expandable over at least 20 passages and retained genome stability and lineage specification potential. Our study therefore establishes a multifunctional route for chemical lineage reprogramming and may provide a platform for generating a diverse range of cell types via application of this expandable XEN-like state.
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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2017.05.019