Depletion of DAND5 Hinders EMT in Mouse Embryonic Stem Cell Differentiation.
Congenital Heart Disease
DAND5.
Epithelial to Mesenchymal Transition
Heart valve development
membrane proteins
stem cell differentiation DAND5
Journal
Current stem cell research & therapy
ISSN: 2212-3946
Titre abrégé: Curr Stem Cell Res Ther
Pays: United Arab Emirates
ID NLM: 101272517
Informations de publication
Date de publication:
16 May 2023
16 May 2023
Historique:
received:
09
12
2022
revised:
01
03
2023
accepted:
07
03
2023
medline:
17
5
2023
pubmed:
17
5
2023
entrez:
17
5
2023
Statut:
aheadofprint
Résumé
Dand5 encodes a protein that acts as an antagonist to Nodal/TGF-β and Wnt pathways. A mouse knockout (KO) model has shown that this molecule is associated with left-right asymmetry and cardiac development, with its depletion causing heterotaxia and cardiac hyperplasia. This study aimed to investigate the molecular mechanisms affected by the depletion of Dand5. DAND5-KO and wild-type embryoid bodies (EBs) were used to assess genetic expression with RNA sequencing. To complement the expression results that pointed towards differences in epithelial to mesenchymal transition (EMT), we evaluated migration and cell attachment. Lastly, in vivo valve development was investigated, as it was an established model of EMT. DAND5-KO EBs progress faster through differentiation. The differences in expression will lead to differences in the expression of genes involved with Notch and Wnt signalling pathways, as well as changes in the expression of genes encoding membrane proteins. Such changes were accompanied by lower migratory rates in DAND5-KO EBs, as well as higher concentrations of focal adhesions. Within valve development, Dand5 is expressed in the myocardium underlying future valve sites, and its depletion compromises correct valve structure. The DAND5 range of action goes beyond early development. Its absence leads to significantly different expression patterns in vitro and defects in EMT and migration. These results have an in vivo translation in mouse heart valve development. Knowledge regarding the influence of DAND5 in EMT and cell transformation allows further understanding of its role in development, or even in some disease contexts, such as congenital heart defects.
Sections du résumé
BACKGROUND
BACKGROUND
Dand5 encodes a protein that acts as an antagonist to Nodal/TGF-β and Wnt pathways. A mouse knockout (KO) model has shown that this molecule is associated with left-right asymmetry and cardiac development, with its depletion causing heterotaxia and cardiac hyperplasia.
OBJECTIVE
OBJECTIVE
This study aimed to investigate the molecular mechanisms affected by the depletion of Dand5.
METHODS
METHODS
DAND5-KO and wild-type embryoid bodies (EBs) were used to assess genetic expression with RNA sequencing. To complement the expression results that pointed towards differences in epithelial to mesenchymal transition (EMT), we evaluated migration and cell attachment. Lastly, in vivo valve development was investigated, as it was an established model of EMT.
RESULTS
RESULTS
DAND5-KO EBs progress faster through differentiation. The differences in expression will lead to differences in the expression of genes involved with Notch and Wnt signalling pathways, as well as changes in the expression of genes encoding membrane proteins. Such changes were accompanied by lower migratory rates in DAND5-KO EBs, as well as higher concentrations of focal adhesions. Within valve development, Dand5 is expressed in the myocardium underlying future valve sites, and its depletion compromises correct valve structure.
CONCLUSION
CONCLUSIONS
The DAND5 range of action goes beyond early development. Its absence leads to significantly different expression patterns in vitro and defects in EMT and migration. These results have an in vivo translation in mouse heart valve development. Knowledge regarding the influence of DAND5 in EMT and cell transformation allows further understanding of its role in development, or even in some disease contexts, such as congenital heart defects.
Identifiants
pubmed: 37194232
pii: CSCR-EPUB-131837
doi: 10.2174/1574888X18666230516154113
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
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