Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure.
Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design.
Biomaterials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan.
Diogo
D
Mosqueira
Stefania
S
Pagliari
Koichiro
K
Uto
Mitsuhiro
M
Ebara
Sara
S
Romanazzo
Carmen
C
Escobedo-Lucea
Jun
J
Nakanishi
Akiyoshi
A
Taniguchi
Ornella
O
Franzese
Paolo
P
Di Nardo
Marie José
MJ
Goumans
Enrico
E
Traversa
Perpetua
P
Pinto-do-Ó
Takao
T
Aoyagi
Giancarlo
G
Forte
D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D001696:Biomechanical Phenomena; D002465:Cell Movement; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D055595:Mechanical Phenomena; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000166:cytology*; D049329:Nanostructures; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases