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TRPML1 ion channel promotes HepaRG cell differentiation under simulated microgravity conditions
Huancai Fan1,2, Dongyuan Lü2,3, Zheng Lu2,3
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, P.R. China.
NPJ Microgravity
|March 16, 2025
Summary
Simulated microgravity promotes hepatic progenitor cell differentiation via the TRPML1 ion channel. This mechanism involves calcium signaling and the Wnt/β-catenin pathway, offering insights into liver development.
Area of Science:
- Cell Biology
- Biophysics
- Developmental Biology
Background:
- Stem cell differentiation is crucial for tissue development, influenced by environmental cues like microgravity.
- Understanding microgravity's effects on cell growth, differentiation, and communication is limited by experimental challenges.
Purpose of the Study:
- To investigate the impact of simulated microgravity on HepaRG (hepatic progenitor) cell differentiation.
- To identify the molecular mechanisms underlying microgravity-induced hepatic cell differentiation.
Main Methods:
- Utilized a Rotating Flat Chamber (RFC) to simulate microgravity on Earth.
- Screened mechanical receptors and signaling pathways involved in cell differentiation.
- Analyzed the expression of hepatic markers (AFP, ALB, CK18) and key signaling molecules.
Main Results:
- Simulated microgravity significantly promoted HepaRG cell differentiation, indicated by increased AFP, ALB, and CK18 expression.
- The ion channel TRPML1 was identified as critical for this differentiation.
- TRPML1 activation led to increased lysosomal calcium, activating the Wnt/β-catenin pathway and promoting differentiation.
Conclusions:
- Simulated microgravity enhances HepaRG cell differentiation through the TRPML1 signaling pathway.
- This pathway involves TRPML1-mediated calcium signaling, Wnt/β-catenin activation, and cytoskeletal remodeling.
- Findings provide a potential target for regulating hepatic stem cell differentiation under microgravity.
