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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
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LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming
Delun Huang1,2, Ling Wang2, Jingyue Duan2
1State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, Guangxi 530004, China.
Biology Open
|December 8, 2017
Summary
Estrogen-related receptor beta (Esrrb) is a key factor in generating induced pluripotent stem cells (iPSCs). Esrrb, regulated by Leukemia inhibitory factor (LIF) signaling, drives pluripotency during reprogramming.
Area of Science:
- Stem cell biology
- Epigenetics and gene regulation
- Developmental biology
Background:
- Naïve-state induced pluripotent stem cell (iPSC) generation regulation is poorly understood.
- Leukemia inhibitory factor (LIF)-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) pathway is crucial for pluripotency.
- Estrogen-related receptor beta (Esrrb) is a marker for naïve pluripotency and ESC self-renewal.
Purpose of the Study:
- To elucidate the interconnection between Esrrb and LIF signaling in pluripotency establishment during reprogramming.
- To identify key marker genes regulated by LIF/Jak signaling during mouse iPSC generation.
- To determine if Esrrb acts downstream of the LIF/Jak pathway.
Main Methods:
- Screening of marker genes involved in complete reprogramming.
- Overexpression of Esrrb in partially reprogrammed cells (pre-iPSCs).
- Inhibition of Jak activity and assessment of Esrrb expression.
- Evaluation of Nanog overexpression and Wnt signaling stimulation effects.
Main Results:
- Esrrb was identified as a gene responsive to LIF/Jak pathway signaling during iPSC generation.
- Esrrb overexpression rescued reprogramming in cells with inhibited Jak activity, leading to pluripotent iPSCs.
- Neither Nanog overexpression nor Wnt signaling stimulation restored Esrrb expression when LIF/Jak was blocked.
Conclusions:
- Esrrb is a specific reprogramming factor acting downstream of the LIF/Jak signaling pathway.
- This finding clarifies the regulatory role of the LIF pathway in achieving complete pluripotency during iPSC generation.
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