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Updated: Dec 9, 2025
09:04
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
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Calreticulin regulates Src kinase in osteogenic differentiation from embryonic stem cells
Zahra Alvandi1, Layla J R Al-Mansoori1, Michal Opas1
1Department of Lab Medicine & Pathobiology, University of Toronto, Toronto, ON M5S1A8, Canada.
Stem Cell Research
|September 11, 2020
Summary
Calreticulin regulates embryonic stem cell differentiation by controlling calcium levels. This pathway involves c-Src kinase and calcineurin, impacting osteogenesis, the process of bone formation.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- Calreticulin is a key calcium-binding protein in the endoplasmic reticulum.
- Embryonic stem cell fate, including osteogenesis, is influenced by intracellular calcium homeostasis.
Purpose of the Study:
- To elucidate the role of calreticulin in embryonic stem cell osteogenic differentiation.
- To identify the signaling pathway linking calreticulin to osteogenesis.
Main Methods:
- Embryoid body formation for organogenesis studies.
- Manipulation of intracellular calcium levels using BAPTA-AM and ionomycin.
- Assessment of c-Src kinase activity and calcineurin phosphatase activity.
- Analysis of Runx2 nuclear translocation.
Main Results:
- Embryonic stem cells lacking calreticulin (crt-/-) exhibited impaired osteogenesis.
- Activated c-Src kinase was observed in crt-/- cells, and its inhibition rescued osteogenesis.
- Calreticulin's calcium-buffering function directly modulated c-Src activity.
- Calcineurin activity was linked to c-Src activity and Runx2 levels, a master regulator of osteogenesis.
Conclusions:
- Calreticulin-dependent calcium signaling via c-Src kinase is a novel pathway regulating embryonic stem cell osteogenic differentiation.
- This pathway involves the downstream effector calcineurin and the transcription factor Runx2.
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