High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy

Jiansen Lu; Jie Ren; Jie Liu; Minjie Lu; Yueli Cui; Yuhan Liao; Yuan Zhou; Yun Gao; Fuchou Tang; Jizheng Wang; Shuiyun Wang; Lu Wen; Lei Song

doi:10.1111/cpr.13557

Cell Proliferation ›› 2024, Vol. 57 ›› Issue (3) :e13557 DOI: 10.1111/cpr.13557

ORIGINAL ARTICLE

High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy

Jiansen Lu ¹^,²
, Jie Ren ¹^,²^,³
, Jie Liu ⁴
, Minjie Lu ⁴
, Yueli Cui ¹^,²
, Yuhan Liao ¹^,²
, Yuan Zhou ¹^,²
, Yun Gao ¹^,²
, Fuchou Tang ¹^,²^,³
, Jizheng Wang ⁴^,^†
, Shuiyun Wang ⁵^,^†
, Lu Wen ¹^,²^,^†
, Lei Song ⁴^,⁶^,⁷^,^†

Author information +

¹. College of Life Sciences, Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China

². Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Peking University, Beijing, China

³. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

⁴. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

⁵. Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

⁶. Cardiomyopathy ward, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

⁷. National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

jzwang@hotmail.com

wsymd@sina.com

wenlu@pku.edu.cn

songlqd@126.com

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Abstract

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, which can cause heart failure and lead to death. In this study, we performed high-resolution single-cell RNA-sequencing of 2115 individual cardiomyocytes obtained from HCM patients and normal controls. Signature up- and down-regulated genes in HCM were identified by integrative analysis across 37 patients and 41 controls from our data and published human single-cell and single-nucleus RNA-seq datasets, which were further classified into gene modules by single-cell co-expression analysis. Using our high-resolution dataset, we also investigated the heterogeneity among individual cardiomyocytes and revealed five distinct clusters within HCM cardiomyocytes. Interestingly, we showed that some extracellular matrix (ECM) genes were up-regulated in the HCM cardiomyocytes, suggesting that they play a role in cardiac remodelling. Taken together, our study comprehensively profiled the transcriptomic programs of HCM cardiomyocytes and provided insights into molecular mechanisms underlying the pathogenesis of HCM.

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Jiansen Lu, Jie Ren, Jie Liu, Minjie Lu, Yueli Cui, Yuhan Liao, Yuan Zhou, Yun Gao, Fuchou Tang, Jizheng Wang, Shuiyun Wang, Lu Wen, Lei Song. High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy. Cell Proliferation, 2024, 57(3): e13557 DOI:10.1111/cpr.13557

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