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NOTCH activity differentially affects alternative cell fate acquisition and maintenance.
Leonard Cheung1, Paul Le Tissier2, Sam Gj Goldsmith3
1Department of Human Genetics, University of Michigan, Ann Arbor, United States.
Elife
|March 27, 2018
Summary
The NOTCH pathway differentially regulates pituitary endocrine cell development. In POMC cells, NOTCH activation blocks differentiation, while POU1F1 cells are unaffected, revealing lineage-specific roles in pituitary plasticity and regeneration.
Area of Science:
- Endocrinology
- Developmental Biology
- Cell Signaling
Background:
- The pituitary gland is crucial for endocrine regulation.
- Understanding endocrine cell fate acquisition is vital for regenerative therapies.
- The NOTCH pathway plays a known role in pituitary development.
Purpose of the Study:
- To investigate the role of the NOTCH pathway in murine pituitary development and cell fate acquisition.
- To determine lineage-specific responses to NOTCH activation in the pituitary.
- To explore the implications for pituitary plasticity and regeneration.
Main Methods:
- Utilized genetic models in mice to activate the NOTCH pathway in progenitor and differentiating pituitary cells.
- Examined the impact of NOTCH activation on cell fate specification in POU1F1 and POMC lineages.
- Assessed the effects of NOTCH signaling on pituitary development and cell plasticity.
Main Results:
- NOTCH activation blocks cell fate acquisition in pituitary progenitors in a time-dependent manner.
- POU1F1 lineage cells show blunted responses to NOTCH activation, with normal cell fate specification.
- POMC lineage cells remain sensitive to NOTCH activation, with NICD inducing a regression to a progenitor-like state, specifically blocking POMC differentiation.
Conclusions:
- The NOTCH pathway exhibits differential sensitivity across pituitary cell lineages.
- NOTCH signaling specifically inhibits POMC cell differentiation, but not POU1F1 cell fate acquisition.
- These findings offer new insights into pituitary development, plasticity, and regenerative potential.
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