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  • YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo.

YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo.

Developmental cell (2019-02-19)
Tanner O Monroe, Matthew C Hill, Yuka Morikawa, John P Leach, Todd Heallen, Shuyi Cao, Peter H L Krijger, Wouter de Laat, Xander H T Wehrens, George G Rodney, James F Martin
ABSTRACT

Specialized adult somatic cells, such as cardiomyocytes (CMs), are highly differentiated with poor renewal capacity, an integral reason underlying organ failure in disease and aging. Among the least renewable cells in the human body, CMs renew approximately 1% annually. Consistent with poor CM turnover, heart failure is the leading cause of death. Here, we show that an active version of the Hippo pathway effector YAP, termed YAP5SA, partially reprograms adult mouse CMs to a more fetal and proliferative state. One week after induction, 19% of CMs that enter S-phase do so twice, CM number increases by 40%, and YAP5SA lineage CMs couple to pre-existing CMs. Genomic studies showed that YAP5SA increases chromatin accessibility and expression of fetal genes, partially reprogramming long-lived somatic cells in vivo to a primitive, fetal-like, and proliferative state.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
OptiPrep Density Gradient Medium, used for cell and subcellular organelle isolation
Supelco
2-[4-(1-Hydroxy-2-methylpropyl)phenyl]propanoic acid, pharmaceutical impurity standard