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In Vitro Generation of Heart Field-specific Cardiac Progenitor Cells
Published on: July 3, 2019
Parietal endoderm secreted SPARC promotes early cardiomyogenesis in vitro
Martina Stary1, Waltraud Pasteiner, Alexandra Summer
1Max F. Perutz Laboratories, University Institutes at the Vienna Biocenter, Department of Medical Biochemistry, Division of Molecular Cell Biology, Medical University of Vienna, Dr. Bohrgasse 9, A1030 Vienna, Austria.
Insights
Secreted Protein, Acidic, Rich in Cysteine (SPARC), secreted by parietal endoderm, promotes early heart cell development. SPARC enhances Bmp2 signaling and Nkx2.5 expression, crucial for cardiomyogenesis.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Cardiovascular Research
Background:
- Cardiomyogenesis, the formation of heart muscle cells, is influenced by extra-embryonic signaling during early development.
- In embryonic stem cell models, parietal endoderm undergoes an epithelial-mesenchymal transition preceding cardiomyocyte contraction.
Purpose of the Study:
- To investigate the role of Secreted Protein, Acidic, Rich in Cysteine (SPARC) in early cardiomyogenesis.
- To elucidate the signaling pathways modulated by SPARC during heart muscle cell differentiation.
Main Methods:
- Utilizing embryonic stem cell-derived embryoid bodies to model early heart development.
- Assessing the impact of SPARC on gene expression (bmp2, nkx2.5) and cardiomyogenesis.
- Employing inhibition studies for SPARC and Bmp2 to determine their functional significance.
Main Results:
- Mesenchymal parietal endoderm secretes SPARC, which promotes myocardial cell differentiation in embryoid bodies.
- SPARC significantly enhanced the expression of bone morphogenetic protein 2 (Bmp2) and NK2 homeobox 5 (Nkx2.5).
- Inhibition of SPARC or Bmp2 attenuated cardiomyogenesis and downregulated Nkx2.5 expression.
Conclusions:
- SPARC directly promotes cardiomyogenesis by modulating Bmp2 signaling.
- SPARC contributes to a positive autoregulatory loop involving Bmp2 and Nkx2.5 in cardiomyocytes.
- These findings highlight SPARC as a key regulator in early heart development.
Abstract:
Cardiomyogenesis proceeds in the presence of signals emanating from extra-embryonic lineages emerging before and during early eutherian gastrulation. In embryonic stem cell derived embryoid bodies, primitive endoderm gives rise to visceral and parietal endoderm. Parietal endoderm undergoes an epithelial to mesenchymal transition shortly before first cardiomyocytes start to contract rhythmically. Here, we demonstrate that Secreted Protein, Acidic, Rich in Cysteine, SPARC, predominantly secreted by mesenchymal parietal endoderm specifically promotes early myocardial cell differentiation in embryoid bodies. SPARC enhanced the expression of bmp2 and nkx2.5 in embryoid bodies and fetal cardiomyocytes. Inhibition of either SPARC or Bmp2 attenuated in both cases cardiomyogenesis and downregulated nkx2.5 expression. Thus, SPARC directly affects cardiomyogenesis, modulates Bmp2 signaling, and contributes to a positive autoregulatory loop of Bmp2 and Nkx2.5 in cardiomyocytes.

