4 years ago

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

Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State
Bingqing Xie, Xiang Li, Hongkui Deng, Ping Zheng, Zhuo Huang, Yanzhong Chang, Weifeng Lai, Xu Zhang, Da Sun, Lipeng Wang, Junzhan Jing, Zhen Chai, Xueqin Jin, Defang Liu, Zexuan Yi, Ting Zhao, Shaoqiang Sun, Xiaomin Du, Jun Xu, Jingyang Guan, Yantao Ma


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.

Publisher URL: http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30185-6

DOI: 10.1016/j.stem.2017.05.019

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