Abstract：
:Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency before establishing the neural fate. We employed genetic lineage tracing and found that induction of iNSCs with individual vectors leads to direct lineage conversion. In contrast, polycistronic expression produces a Brn4-Klf4 fusion protein that enables induction of pluripotency. Our study demonstrates that a combination of pluripotency and tissue-specific factors allows direct somatic cell transdifferentiation, bypassing the acquisition of a pluripotent state. This result has major implications for lineage conversion technologies, which hold potential for providing a safer alternative to iPSCs for clinical application both in vitro and in vivo.
journal_name
Cell Repjournal_title
Cell reportsauthors
Velychko S,Kang K,Kim SM,Kwak TH,Kim KP,Park C,Hong K,Chung C,Hyun JK,MacCarthy CM,Wu G,Schöler HR,Han DWdoi
10.1016/j.celrep.2019.03.023subject
Has Abstractpub_date
2019-04-02 00:00:00pages
30-39.e4issue
1issn
2211-1247pii
S2211-1247(19)30339-0journal_volume
27pub_type
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