Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate.
Ana G Freire1, Avinash Waghray2, Francisca Soares-da-Silva3
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; Department of Cell, Developmental and Regenerative Biology and The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal.
Stem Cell Reports
|June 27, 2017
Summary
The Notch pathway
Area of Science:
- Developmental biology
- Stem cell biology
- Molecular biology
Background:
- Notch signaling is crucial for cardiac fate specification.
- Downstream effectors of Notch in cardiogenesis are largely unknown.
Purpose of the Study:
- To investigate the role of HES5, a Notch downstream effector, in early heart development (cardiogenesis).
- To elucidate HES5's function in cardiac versus primitive erythroid cell fate determination.
Main Methods:
- Analysis of Hes5 expression during mouse embryonic development.
- Loss- and gain-of-function studies using mouse embryonic stem cells.
- Gene expression analysis of cardiac and hematopoietic markers (e.g., Isl1, Scl).
Main Results:
- Transient Hes5 expression observed in early mesoderm during gastrulation.
- HES5 overexpression favored cardiac over erythroid fate in stem cells.
- Hes5 promoted cardiac gene Isl1 upregulation and Scl downregulation.
- A transient pulse of Hes5 induced cardiac commitment.
- Sustained Hes5 expression hindered cardiomyocyte differentiation progression.
Conclusions:
- HES5 is implicated as a key regulator in early cardiogenesis.
- Hes5 acts as a critical determinant of cardiac versus erythroid lineage.
- The timing of Hes5 expression is crucial for proper cardiac differentiation.
