Single-cell transcriptomics provides insights into hypertrophic cardiomyopathy
Wehrens, Martijn; de Leeuw, Anne E.; Wright-Clark, Maya; Eding, Joep E.C.; Boogerd, Cornelis J.; Molenaar, Bas; van der Kraak, Petra H.; Kuster, Diederik W.D.; van der Velden, Jolanda; Michels, Michelle; Vink, Aryan; van Rooij, Eva
(2022) Cell Reports, volume 39, issue 6, pp. 1 - 22
(Article)
Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic heart disease that is characterized by unexplained segmental hypertrophy that is usually most pronounced in the septum. While sarcomeric gene mutations are often the genetic basis for HCM, the mechanistic origin for the heterogeneous remodeling remains largely unknown. A better understanding of the gene
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networks driving the cardiomyocyte (CM) hypertrophy is required to improve therapeutic strategies. Patients suffering from HCM often receive a septal myectomy surgery to relieve outflow tract obstruction due to hypertrophy. Using single-cell RNA sequencing (scRNA-seq) on septal myectomy samples from patients with HCM, we identify functional links between genes, transcription factors, and cell size relevant for HCM. The data show the utility of using scRNA-seq on the human hypertrophic heart, highlight CM heterogeneity, and provide a wealth of insights into molecular events involved in HCM that can eventually contribute to the development of enhanced therapies.
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Keywords: cardiomyocyte, cell size, CP: Molecular biology, flow cytometry, HCM, hypertrophic cardiomyopathy, myectomy, scRNA-seq, sequencing, single cell, Cardiomyopathy, Hypertrophic/genetics, Humans, Transcriptome/genetics, Heart Defects, Congenital, Sarcomeres, Hypertrophy, General Biochemistry,Genetics and Molecular Biology, Journal Article
ISSN: 2211-1247
Publisher: Cell Press
Note: Funding Information: We gratefully acknowledge Roy Huurman, Sylvie Dekker, Martine de Boer, Harm de Wit, and Peter van Geel from the Erasmus Medical Center for facilitating sample collection and help with flow cytometry. We thank Stefan van der Elst from the Hubrecht Institute FACS facility for his help with the viability experiments and presenting our flow cytometry data, Jeroen Korving for his help with histology, and Anna Alemany for her help with mapping raw data. We further thank Anko de Graaff and the Hubrecht Imaging Center for supporting the imaging. Last, we acknowledge Cris dos Remedios for providing us donor heart samples from the Sydney Heart Bank. This work was supported by the Leducq Foundation ( 14CVD04 ), the European Research Council under the European Union's Seventh Framework Program ( ERC Grant Agreement CoG 615708 MICARUS), and the Dutch Cardiovascular Alliance ( DCVA ), an initiative with support of the Dutch Heart Foundation , DCVA2017-18 ARENA-PRIME and DCVA2014-40 CVON-DOSIS . Funding Information: We gratefully acknowledge Roy Huurman, Sylvie Dekker, Martine de Boer, Harm de Wit, and Peter van Geel from the Erasmus Medical Center for facilitating sample collection and help with flow cytometry. We thank Stefan van der Elst from the Hubrecht Institute FACS facility for his help with the viability experiments and presenting our flow cytometry data, Jeroen Korving for his help with histology, and Anna Alemany for her help with mapping raw data. We further thank Anko de Graaff and the Hubrecht Imaging Center for supporting the imaging. Last, we acknowledge Cris dos Remedios for providing us donor heart samples from the Sydney Heart Bank. This work was supported by the Leducq Foundation (14CVD04), the European Research Council under the European Union's Seventh Framework Program (ERC Grant Agreement CoG 615708 MICARUS), and the Dutch Cardiovascular Alliance (DCVA), an initiative with support of the Dutch Heart Foundation, DCVA2017-18 ARENA-PRIME and DCVA2014-40 CVON-DOSIS. J.E.C.E. A.E.L. M.W.C. and E.R. designed and performed experiments. M.W. J.E.C.E. C.J.B. and B.M. analyzed the data. P.K. D.K. J.V. M.M. and A.V. provided resources and methodologies J.E.C.E. A.E.L. M.W.C. M.W. and E.R wrote the manuscript. E.R. acquired funding. The authors declare no competing interests. Publisher Copyright: © 2022 Copyright © 2022. Published by Elsevier Inc.
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