@article{791e466665564504bd2d64aca68d60d3,
title = "Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy",
abstract = "Diabetes is associated with a significantly elevated risk of heart failure. However, despite extensive efforts to characterize the phenotype of the diabetic heart, the molecular and cellular protagonists that underpin cardiac pathological remodeling in diabetes remain unclear, with a notable paucity of data regarding the impact of diabetes on non-myocytes within the heart. Here we aimed to define key differences in cardiac non-myocytes between spontaneously type-2 diabetic (db/db) and healthy control (db/h) mouse hearts. Single-cell transcriptomic analysis revealed a concerted diabetes-induced cellular response contributing to cardiac remodeling. These included cell-specific activation of gene programs relating to fibroblast hyperplasia and cell migration, and dysregulation of pathways involving vascular homeostasis and protein folding. This work offers a new perspective for understanding the cellular mediators of diabetes-induced cardiac pathology, and pathways that may be targeted to address the cardiac complications associated with diabetes.",
keywords = "Cell biology, Molecular biology, Omics, Transcriptomics",
author = "Cohen, {Charles D.} and {De Blasio}, {Miles J.} and Farrugia, {Gabriella E.} and Dona, {Malathi S.I.} and Ian Hsu and Darnel Prakoso and Helen Kiriazis and Crisdion Krstevski and Nash, {David M.} and Mandy Li and Gaynor, {Taylah L.} and Minh Deo and Drummond, {Grant R.} and Ritchie, {Rebecca H.} and Pinto, {Alexander R.}",
note = "Funding Information: ARP and RHR received supported from the National Health and Medical Research Council (NHMRC) of Australia, including Ideas Grant GNT1188503 to ARP, Project Grant GNT 1158013 to RHR and MJD, and Senior Research Fellowship GNT1059960 to RHR. CDC, CK and TLG are supported by the La Trobe University Postgraduate Research Scholarship (LTUPRS), Research Training Program Fees Off-set (RTP-Fo) Scholarship. CDC is also supported by a Baker Institute “Bright Sparks” Scholarship and Harold Mitchell Foundation Scholarship. TLG is also supported by a Defence Science Institute RhD Grant. The work was also supported in part by an infrastructure grant from the Victorian Government of Australia. CDC, MJD, RHR, and ARP conceived the study. RHR, MJD and ARP obtained funding for, and oversaw, the study. CDC and ARP drafted the article. CDC, MJD, MD, and DP performed animal monitoring. CDC and MJD assisted with in vivo echocardiography. Echocardiographic imaging was acquired by HK. CDC analyzed echocardiography data. MJD and HK reviewed echocardiography analyses. CDC, MJD, GEF, DP, CK, DMN, ML, TLG, MD, and ARP performed endpoint cull experiments. CDC, IH, MSID, and ARP analyzed in silico transcriptomic data. CDC, MJD, GRD, RHR, and ARP regularly reviewed and interpreted the results obtained as they were acquired. All authors read, edited and agreed to submission of the final version of the article. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: ARP and RHR received supported from the National Health and Medical Research Council (NHMRC) of Australia, including Ideas Grant GNT1188503 to ARP, Project Grant GNT 1158013 to RHR and MJD, and Senior Research Fellowship GNT1059960 to RHR. CDC, CK and TLG are supported by the La Trobe University Postgraduate Research Scholarship (LTUPRS), Research Training Program Fees Off-set (RTP-Fo) Scholarship . CDC is also supported by a Baker Institute “Bright Sparks” Scholarship and Harold Mitchell Foundation Scholarship . TLG is also supported by a Defence Science Institute RhD Grant. The work was also supported in part by an infrastructure grant from the Victorian Government of Australia . Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = oct,
day = "20",
doi = "10.1016/j.isci.2023.107759",
language = "English",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "10",
}
