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

First Author  Li X Year  2017
Journal  Cell Stem Cell Volume  21
Issue  2 Pages  264-273.e7
PubMed ID  28648365 Mgi Jnum  J:253977
Mgi Id  MGI:6101292 Doi  10.1016/j.stem.2017.05.019
Citation  Li X, et al. (2017) Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State. Cell Stem Cell 21(2):264-273.e7
abstractText  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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