@article{bb1aa7bd20724e9c9d1db323ca97af3c,
title = "Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation",
abstract = "Sex disparities in cardiac homeostasis and heart disease are well documented, with differences attributed to actions of sex hormones. However, studies have indicated sex chromosomes act outside of the gonads to function without mediation by gonadal hormones. Here, we performed transcriptional and proteomics profiling to define differences between male and female mouse hearts. We demonstrate, contrary to current dogma, cardiac sex disparities are controlled not only by sex hormones but also through a sex-chromosome mechanism. Using Turner syndrome (XO) and Klinefelter (XXY) models, we find the sex-chromosome pathway is established by X-linked gene dosage. We demonstrate cardiac sex disparities occur at the earliest stages of heart formation, a period before gonad formation. Using these datasets, we identify and define a role for alpha-1B-glycoprotein (A1BG), showing loss of A1BG leads to cardiac defects in females, but not males. These studies provide resources for studying sex-biased cardiac disease states.",
keywords = "A1BG, cardiac sex differences, gonadal hormones, proteomics, sex chromosomes",
author = "Wei Shi and Xinlei Sheng and Dorr, {Kerry M.} and Hutton, {Josiah E.} and Emerson, {James I.} and Davies, {Haley A.} and Andrade, {Tia D.} and Wasson, {Lauren K.} and Greco, {Todd M.} and Yutaka Hashimoto and Federspiel, {Joel D.} and Robbe, {Zachary L.} and Xuqi Chen and Arnold, {Arthur P.} and Cristea, {Ileana M.} and Conlon, {Frank L.}",
note = "Funding Information: This work was supported by grants R01HD089275 NIH/NHLBI and R01HL127640 NIH/NHLBI to F.L.C. and I.M.C. W.S. X.S. I.M.C. and F.L.C. designed and interpreted the experiments. W.S. X.S. K.M.D. J.E.H. J.I.E. H.A.D. T.D.A. and X.C. performed the experiments. W.S. X.S. J.E.H. J.I.E. T.M.G. Y.H. J.D.F. L.K.W. Z.L.R. A.P.A. I.M.C. and F.L.C. analyzed the data. W.S. X.S. J.E.H. T.M.G. A.P.A. I.M.C. and F.L.C. wrote the paper. The authors declare no competing interests. All affiliations are listed on the title page of the manuscript. All funding sources for this study are listed in the acknowledgments section of the manuscript. The authors and their immediate family members, have no financial interests or related patents to declare. The authors and their immediate family members have no positions to declare and are not members of the journal's advisory board. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the genomic datasets. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = nov,
day = "8",
doi = "10.1016/j.devcel.2021.09.022",
language = "English (US)",
volume = "56",
pages = "3019--3034.e7",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "21",
}