Imperial College London
Alternate

Emeritus ProfessorMichaelSchneider

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor in Cardiology
 
 
 
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Contact

 

+44 (0)013 34621727m.d.schneider Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Adamowicz:2018:10.1161/CIRCGEN.117.001805,
author = {Adamowicz, M and Morgan, CC and Haubner, BJ and Noseda, M and Collins, MJ and Paiva, MA and Srivastava, PK and Gellert, P and Razzaghi, B and O'Gara, P and Raina, P and Game, L and Bottolo, L and Schneider, MD and Harding, SE and Penninger, J and Aitman, TJ},
doi = {10.1161/CIRCGEN.117.001805},
journal = {Circulation: Cardiovascular Genetics},
title = {Functionally conserved noncoding regulators of cardiomyocyte proliferation and regeneration in mouse and human},
url = {http://dx.doi.org/10.1161/CIRCGEN.117.001805},
volume = {11},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: The adult mammalian heart has little regenerative capacity after myocardial infarction (MI), whereas neonatal mouse heart regenerates without scarring or dysfunction. However, the underlying pathways are poorly defined. We sought to derive insights into the pathways regulating neonatal development of the mouse heart and cardiac regeneration post-MI.Methods and Results: Total RNA-seq of mouse heart through the first 10 days of postnatal life (referred to as P3, P5, P10) revealed a previously unobserved transition in microRNA (miRNA) expression between P3 and P5 associated specifically with altered expression of protein-coding genes on the focal adhesion pathway and cessation of cardiomyocyte cell division. We found profound changes in the coding and noncoding transcriptome after neonatal MI, with evidence of essentially complete healing by P10. Over two-thirds of each of the messenger RNAs, long noncoding RNAs, and miRNAs that were differentially expressed in the post-MI heart were differentially expressed during normal postnatal development, suggesting a common regulatory pathway for normal cardiac development and post-MI cardiac regeneration. We selected exemplars of miRNAs implicated in our data set as regulators of cardiomyocyte proliferation. Several of these showed evidence of a functional influence on mouse cardiomyocyte cell division. In addition, a subset of these miRNAs, miR-144-3p, miR-195a-5p, miR-451a, and miR-6240 showed evidence of functional conservation in human cardiomyocytes.Conclusions: The sets of messenger RNAs, miRNAs, and long noncoding RNAs that we report here merit further investigation as gatekeepers of cell division in the postnatal heart and as targets for extension of the period of cardiac regeneration beyond the neonatal period.
AU  - Adamowicz,M
AU  - Morgan,CC
AU  - Haubner,BJ
AU  - Noseda,M
AU  - Collins,MJ
AU  - Paiva,MA
AU  - Srivastava,PK
AU  - Gellert,P
AU  - Razzaghi,B
AU  - O'Gara,P
AU  - Raina,P
AU  - Game,L
AU  - Bottolo,L
AU  - Schneider,MD
AU  - Harding,SE
AU  - Penninger,J
AU  - Aitman,TJ
DO  - 10.1161/CIRCGEN.117.001805
PY  - 2018///
SN  - 1942-325X
TI  - Functionally conserved noncoding regulators of cardiomyocyte proliferation and regeneration in mouse and human
T2  - Circulation: Cardiovascular Genetics
UR  - http://dx.doi.org/10.1161/CIRCGEN.117.001805
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000426177700003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/57815
VL  - 11
ER  -
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