Polo‐Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes‐Associated Protein 1 in Cardiac Progenitor Cells

Autor: Anna Marsano, Emanuele Gaudiello, Robert Ivanek, Otmar Pfister, Gabriela M. Kuster, Vera Lorenz, Giacomo Della Verde, Michika Mochizuki
Rok vydání: 2017
Předmět:
0301 basic medicine
Time Factors
Cell Cycle Proteins
Polo-like kinase
Molecular Cardiology
Rats
Sprague-Dawley
Extracellular matrix
0302 clinical medicine
polo‐like kinase 2
Medicine
Myocytes
Cardiac
Cells
Cultured
Endothelial Progenitor Cells
Original Research
cell fate
Stem Cells
Gene Expression Regulation
Developmental
Cell Differentiation
Cell biology
Phenotype
RNA Interference
Yes‐associated protein
Cardiology and Cardiovascular Medicine
Signal Transduction
Cardiac progenitors
extracellular matrix
Neovascularization
Physiologic
cardiac progenitor cells
Mice
Transgenic
Protein Serine-Threonine Kinases
Cell fate determination
Transfection
Lineage specification
Yes associated protein 1
03 medical and health sciences
Downstream (manufacturing)
Cell Adhesion
Animals
Cell Lineage
Progenitor cell
Adaptor Proteins
Signal Transducing
Cell Proliferation
business.industry
YAP-Signaling Proteins
Phosphoproteins
Coculture Techniques
Fibronectins
030104 developmental biology
Laminin
Apoptosis Regulatory Proteins
business
Basic Science Research
Cell Signalling/Signal Transduction
030217 neurology & neurosurgery
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
DOI: 10.1161/jaha.117.005920
Popis: Background Recent studies suggest that adult cardiac progenitor cells ( CPC s) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPC s are ill defined. Methods and Results Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (YAP ) conserved signature and TEA domain family member 1 (TEAD1)‐related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo‐like kinase 2 ( Plk2 ). Plk2 expression depended on YAP stability and was enhanced in CPC s transfected with a nuclear‐targeted mutant YAP . Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Conclusions Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPC s. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated.
Databáze: OpenAIRE
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