单细胞 RNA 测序在缺血性心肌病中揭示了终末期心力衰竭的常见转录谱。

Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure.

机构信息

Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.

出版信息

Cell Rep. 2023 Feb 28;42(2):112086. doi: 10.1016/j.celrep.2023.112086. Epub 2023 Feb 14.

DOI:10.1016/j.celrep.2023.112086

PMID:36790929

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10423750/

Abstract

Ischemic cardiomyopathy (ICM) is the leading cause of heart failure worldwide, yet the cellular and molecular signature of this disease is largely unclear. Using single-nucleus RNA sequencing (snRNA-seq) and integrated computational analyses, we profile the transcriptomes of over 99,000 human cardiac nuclei from the non-infarct region of the left ventricle of 7 ICM transplant recipients and 8 non-failing (NF) controls. We find the cellular composition of the ischemic heart is significantly altered, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in patients with ICM. We show that there is increased LAMININ signaling from endothelial cells to other cell types in ICM compared with NF. Finally, we find that the transcriptional changes that occur in ICM are similar to those in hypertrophic and dilated cardiomyopathies and that the mining of these combined datasets can identify druggable genes that could be used to target end-stage heart failure.

摘要

缺血性心肌病（ICM）是全球心力衰竭的主要病因，但这种疾病的细胞和分子特征在很大程度上尚不清楚。我们使用单核 RNA 测序（snRNA-seq）和综合计算分析，对 7 名 ICM 移植受者和 8 名非衰竭（NF）对照的左心室非梗死区的超过 99000 个人类心脏核的转录组进行了分析。我们发现缺血性心脏的细胞组成发生了显著改变，ICM 患者的心肌细胞减少，淋巴管生成、血管生成和动脉内皮细胞的比例增加。我们表明，与 NF 相比，ICM 中内皮细胞向其他细胞类型发出的层粘连蛋白信号增加。最后，我们发现 ICM 中发生的转录变化与肥厚性和扩张性心肌病相似，并且挖掘这些组合数据集可以识别可用于靶向终末期心力衰竭的可用药基因。