小柯机器人

德国慕尼黑工业大学Alessandra Moretti课题组发现，心外膜类器官单细胞基因组学揭示心脏发育和疾病中的人类心外膜生物学原理。相关论文于2023年4月3日在线发表在《自然—生物技术》杂志上。

研究人员产生了自组织的人类多能干细胞衍生的心外膜类器官，显示出视黄酸依赖的心外膜和心肌的形态、分子和功能模式，并且是左心室壁的典型。通过结合系谱追踪、单细胞转录组学和染色质可及性分析，研究人员描述了心外膜中不同细胞系的特化和分化过程，并在转录和形态水平上与人类胎儿发育进行了比较。然后，研究人员利用心外膜类器官来研究了心脏细胞类型之间的功能交叉，对IGF2/IGF1R和NRP2信号在人类心脏发生中的作用有了新的认识。

最后，研究人员表明，心外膜类器官模拟了先天性或压力引起的肥大和纤维化重塑的多细胞发病机制。因此，心外膜类器官为心脏发育、疾病和再生中的心外膜活动提供了一个独特的试验场。

研究人员表示，心外膜是脊椎动物心脏的间皮包膜，是胚胎发育过程中多个心脏细胞系的来源，并提供对心肌生长和修复至关重要的信号。

附：英文原文

Title: Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease

Author: Meier, Anna B., Zawada, Dorota, De Angelis, Maria Teresa, Martens, Laura D., Santamaria, Gianluca, Zengerle, Sophie, Nowak-Imialek, Monika, Kornherr, Jessica, Zhang, Fangfang, Tian, Qinghai, Wolf, Cordula M., Kupatt, Christian, Sahara, Makoto, Lipp, Peter, Theis, Fabian J., Gagneur, Julien, Goedel, Alexander, Laugwitz, Karl-Ludwig, Dorn, Tatjana, Moretti, Alessandra

Issue&Volume: 2023-04-03

Abstract: The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.

DOI: 10.1038/s41587-023-01718-7

Source: https://www.nature.com/articles/s41587-023-01718-7

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex