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Updated: Aug 24, 2026
Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
Calcineurin initiates smooth muscle differentiation in neural crest stem cells
Kris M Mann1, Jenna Lynn Ray, Edward S Moon
17301E MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109, USA.
Abstract:
The process of vascular smooth muscle cell (vSMC) differentiation is critical to embryonic angiogenesis. However, despite its importance, the vSMC differentiation program remains largely undefined. Murine gene disruption studies have identified several gene products that are necessary for vSMC differentiation, but these methodologies cannot establish whether or not a factor is sufficient to initiate the differentiation program. A gain-of-function system consisting of normal vSMC progenitor cells would serve as a useful complement to whole animal loss-of-function studies. We use such a system here, namely freshly isolated rat neural crest stem cells (NCSCs), to show that activation of the calcineurin signaling pathway is sufficient to drive these cells toward a smooth muscle fate. In addition, we present data suggesting that transforming growth factor (TGF)-beta1, which also causes NCSCs to differentiate into smooth muscle, activates calcineurin signaling in NCSCs, leading to a model in which activation of calcineurin signaling is the mechanism by which TGF-beta1 causes SMC differentiation in these cells.
Insights
Activating calcineurin signaling is sufficient to induce neural crest stem cells to become vascular smooth muscle cells. Transforming growth factor-beta1 also drives this differentiation by activating calcineurin signaling.
Area of Science:
- Developmental biology
- Cell biology
- Stem cell research
Background:
- Vascular smooth muscle cell (vSMC) differentiation is crucial for embryonic blood vessel formation (angiogenesis).
- The precise molecular mechanisms governing vSMC differentiation remain incompletely understood.
- Previous studies using gene knockout models identified necessary factors but couldn't determine sufficiency for initiating differentiation.
Purpose of the Study:
- To establish a gain-of-function system to study vSMC differentiation.
- To determine if calcineurin signaling activation is sufficient to induce smooth muscle cell fate.
- To investigate the role of transforming growth factor-beta1 (TGF-β1) in vSMC differentiation.
Main Methods:
- Utilized freshly isolated rat neural crest stem cells (NCSCs) as a model system.
- Investigated the effects of activating the calcineurin signaling pathway on NCSC differentiation.
- Examined the impact of TGF-β1 on NCSC differentiation and its effect on calcineurin signaling.
Main Results:
- Activation of the calcineurin signaling pathway was sufficient to drive NCSCs toward a smooth muscle cell fate.
- TGF-β1 treatment also induced smooth muscle differentiation in NCSCs.
- Data suggest TGF-β1 activates calcineurin signaling in NCSCs, mediating smooth muscle differentiation.
Conclusions:
- Calcineurin signaling activation is a sufficient trigger for inducing smooth muscle cell differentiation from progenitor cells.
- TGF-β1 likely promotes smooth muscle cell differentiation through the calcineurin signaling pathway.
- This study provides a novel gain-of-function model for understanding vSMC differentiation.
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