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TGF? signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells.


ABSTRACT: Human urine cells (HUCs) can be reprogrammed into neural progenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) with defined factors and a small molecule cocktail, but the underlying fate choice remains unresolved. Here, through sequential removal of individual compound from small molecule cocktail, we showed that A8301, a TGF? signaling inhibitor, is sufficient to switch the cell fate from iPSCs into NPCs in OSKM-mediated HUCs reprogramming. However, TGF? exposure at early stage inhibits HUCs reprogramming by promoting EMT. Base on these data, we developed an optimized approach for generation of NPCs or iPSCs from HUCs with significantly improved efficiency by regulating TGF? activity at different reprogramming stages. This approach provides a simplified and improved way for HUCs reprogramming, thus would be valuable for banking human iPSCs or NPCs from people with different genetic background.

SUBMITTER: Wang L 

PROVIDER: S-EPMC4776143 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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TGFβ signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells.

Wang Lihui L   Li Xirui X   Huang Wenhao W   Zhou Tiancheng T   Wang Haitao H   Lin Aiping A   Hutchins Andrew Paul AP   Su Zhenghui Z   Chen Qianyu Q   Pei Duanqing D   Pan Guangjin G  

Scientific reports 20160303


Human urine cells (HUCs) can be reprogrammed into neural progenitor cells (NPCs) or induced pluripotent stem cells (iPSCs) with defined factors and a small molecule cocktail, but the underlying fate choice remains unresolved. Here, through sequential removal of individual compound from small molecule cocktail, we showed that A8301, a TGFβ signaling inhibitor, is sufficient to switch the cell fate from iPSCs into NPCs in OSKM-mediated HUCs reprogramming. However, TGFβ exposure at early stage inhi  ...[more]

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