LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming

The regulatory process of naïve-state induced pluripotent stem cell (iPSC) generation is not well understood. Leukemia inhibitory factor (LIF)-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and ma...

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Bibliographic Details
Published in:Biology open 2018-01, Vol.7 (1), p.bio029264-bio029264
Main Authors: Huang, Delun, Wang, Ling, Duan, Jingyue, Huang, Chang, Tian, Xiuchun Cindy, Zhang, Ming, Tang, Young
Format: Article
Language:English
Subjects:
Biomarkers
Cell self-renewal
Downstream effects
Embryo cells
Embryos
Esrrb
Estrogens
Genes
Inhibitory postsynaptic potentials
iPSC
Jak
Janus kinase
Kinases
Leukemia
Leukemia inhibitory factor
LIF
Pluripotency
Regulators
Reprogramming
Signal transduction
Signaling
Stat3 protein
Stem cell transplantation
Stem cells
Transcription
Wnt protein
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Summary:The regulatory process of naïve-state induced pluripotent stem cell (iPSC) generation is not well understood. Leukemia inhibitory factor (LIF)-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta ( ) serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs). However, the interconnection between and LIF signaling for pluripotency establishment in reprogramming is unclear. We screened the marker genes critical for complete reprogramming during mouse iPSC generation, and identified genes including that are responsive to LIF/Jak pathway signaling. Overexpression of resumes the reprogramming halted by inhibition of Jak activity in partially reprogrammed cells (pre-iPSCs), and leads to the generation of pluripotent iPSCs. We further show that neither overexpression of nor stimulation of Wnt signaling, two upstream regulators of in ESCs, stimulates the expression of in reprogramming when LIF or Jak activity is blocked. Our study demonstrates that is a specific reprogramming factor regulated downstream of the LIF/Jak signaling pathway. These results shed new light on the regulatory role of LIF pathway on complete pluripotency establishment during iPSC generation.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.029264