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科学家完成先天性心脏病的综合多组学表征
2022-06-26 15:14
来源：小柯机器人

美国贝勒医学院James F. Martin研究团队完成先天性心脏病的综合多组学表征。该项研究成果于2022年6月22日在线发表在《自然》杂志上。

研究人员表示，心脏是第一个发育的器官，经历了复杂的形态发生，一旦出现缺陷，就会导致先天性心脏病（CHD）。在目前的治疗方法下，90%以上的CHD患者能存活到成年，但往往因心力衰竭（HF）和非心脏原因而过早死亡。
 
为了深入了解不为人知的疾病进展，研究人员进行了单核RNA测序（snRNA-seq），并分析了157,273个来自捐赠者和CHD患者的细胞核，包括发育不全左心综合征（HLHS）和法洛氏四联症（TOF），两种常见的CHD病变形式，以及扩张型（DCM）和肥厚型（HCM）心肌病。研究人员观察到心肌细胞（CM）的CHD特定细胞状态，这些细胞有胰岛素抵抗的证据，FOXO和CRIM1表达增加。HLHS的心脏成纤维细胞（CF）富集了低HIPPO和高YAP的细胞状态，这是激活CF的特征。成像质谱仪（IMC）发现了与CHD免疫缺陷状态相一致的血管周围微环境的空间分辨率。
 
外围免疫细胞分析表明，CHD的单核细胞免疫功能不足，与CHD对感染和癌症的偏好一致。这个全面的CHD表型为未来CHD的个性化医疗提供了一个路线图。
 
附：英文原文
 
Title: Integrated multiomic characterization of congenital heart disease

Author: Hill, Matthew C., Kadow, Zachary A., Long, Hali, Morikawa, Yuka, Martin, Thomas J., Birks, Emma J., Campbell, Kenneth S., Nerbonne, Jeanne, Lavine, Kory, Wadhwa, Lalita, Wang, Jun, Turaga, Diwakar, Adachi, Iki, Martin, James F.

Issue&Volume: 2022-06-22

Abstract: The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes 1. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq) and analyzed 157,273 nuclei from donors and CHD patients, including hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF), two common forms of cyanotic CHD lesions, as well as, dilated (DCM) and hypertrophic (HCM) cardiomyopathies. We observed CHD specific cell states in cardiomyocytes (CMs) which had evidence of insulin resistance and increased FOXO and CRIM1 expression. Cardiac fibroblasts (CFs) in HLHS had enrichment for a low HIPPO and high YAP cell state characteristic of activated CFs. Imaging Mass Cytometry (IMC) uncovered the spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD in agreement with CHD predilection to infection and cancer 2. Our comprehensive CHD phenotyping provides a roadmap for future personalized medicine in CHD.

DOI: 10.1038/s41586-022-04989-3

Source: https://www.nature.com/articles/s41586-022-04989-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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