Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State
| Autor: | Zexuan Yi, Zhen Chai, Defang Liu, Da Sun, Ping Zheng, Xiaomin Du, Junzhan Jing, Ting Zhao, Weifeng Lai, Zhuo Huang, Yantao Ma, Yanzhong Chang, Hongkui Deng, Jun Xu, Lipeng Wang, Xueqin Jin, Xiang Li, Xu Zhang, Shaoqiang Sun, Jingyang Guan, Bingqing Xie |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cell type Aging Lineage (genetic) Transcription Genetic Cell Survival Green Fluorescent Proteins Induced Pluripotent Stem Cells Extraembryonic Membranes Biology Bioinformatics Genomic Instability 03 medical and health sciences Mice Genetics medicine Animals Cell Lineage Induced pluripotent stem cell Cells Cultured Genome stability Neurons Gene Expression Profiling Endoderm Brain Cell Differentiation Cell Biology Fibroblasts Cellular Reprogramming Small molecule Cell biology Transplantation 030104 developmental biology medicine.anatomical_structure Animals Newborn Molecular Medicine Female Reprogramming |
| Zdroj: | Cell stem cell. 21(2) |
| ISSN: | 1875-9777 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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