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TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies
- Source :
- Stem Cells and Development, Stem Cells and Development, Mary Ann Liebert, 2012, 21 (17), pp.3081-90. ⟨10.1089/scd.2012.0277⟩
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- International audience; Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.
- Subjects :
- Cellular differentiation
Biopsy
Myocardial Ischemia
Fluorescent Antibody Technique
MESH: Myocytes, Cardiac
030204 cardiovascular system & hematology
MESH: Receptor, Notch1
Regenerative medicine
MESH: Benzamides
MESH: Biopsy
0302 clinical medicine
Transforming Growth Factor beta
Myocytes, Cardiac
MESH: Dioxoles
Receptor, Notch1
MESH: Fluorescent Antibody Technique
Cells, Cultured
0303 health sciences
Cutting-Edge Communications
Stem Cells
MESH: Regeneration
Cell Differentiation
Hematology
MESH: Transcription Factors
MESH: Gene Expression Regulation
Cell biology
Benzamides
MESH: Myocardial Ischemia
MESH: Receptors, Transforming Growth Factor beta
Stem cell
MESH: Cells, Cultured
Adult
MESH: Cell Differentiation
Epithelial-Mesenchymal Transition
MESH: Myocardium
Dioxoles
MESH: Stem Cells
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
03 medical and health sciences
MESH: Gene Expression Profiling
Humans
Regeneration
epithelial-to-mesenchymal transition
TGF-beta
cardiac progenitor cells
Epithelial–mesenchymal transition
MESH: Transforming Growth Factor beta
030304 developmental biology
MESH: Humans
Regeneration (biology)
Gene Expression Profiling
Myocardium
MESH: Biological Markers
MESH: Adult
Cell Biology
Transforming growth factor beta
MESH: Epithelial-Mesenchymal Transition
Gene Expression Regulation
Immunology
biology.protein
Snail Family Transcription Factors
Receptors, Transforming Growth Factor beta
Ex vivo
Biomarkers
Developmental Biology
Transforming growth factor
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 15473287
- Database :
- OpenAIRE
- Journal :
- Stem Cells and Development, Stem Cells and Development, Mary Ann Liebert, 2012, 21 (17), pp.3081-90. ⟨10.1089/scd.2012.0277⟩
- Accession number :
- edsair.doi.dedup.....138f946af331f34f681163363b9ed600