Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Instituto Nacional de Engenharia Biomédica (INEB), Universidade do Porto, Porto, Portugal.
PLoS Biol. 2019 Jun 27;17(6):e3000335. doi: 10.1371/journal.pbio.3000335. eCollection 2019 Jun.
The assessment of the regenerative capacity of the heart has been compromised by the lack of surface signatures to characterize cardiomyocytes (CMs). Here, combined multiparametric surface marker analysis with single-cell transcriptional profiling and in vivo transplantation identify the main mouse fetal cardiac populations and their progenitors (PRGs). We found that CMs at different stages of differentiation coexist during development. We identified a population of immature heat stable antigen (HSA)/ cluster of differentiation 24 (CD24)+ CMs that persists throughout life and that, unlike other CM subsets, actively proliferates up to 1 week of age and engrafts cardiac tissue upon transplantation. In the adult heart, a discrete population of HSA/CD24+ CMs appears as mononucleated cells that increase in frequency after infarction. Our work identified cell surface signatures that allow the prospective isolation of CMs at all developmental stages and the detection of a subset of immature CMs throughout life that, although at reduced frequencies, are poised for activation in response to ischemic stimuli. This work opens new perspectives in the understanding and treatment of heart pathologies.
心脏的再生能力评估一直受到缺乏表面特征来表征心肌细胞（CMs）的限制。在这里，结合多参数表面标志物分析与单细胞转录组分析和体内移植，确定了主要的小鼠胎儿心脏群体及其祖细胞（PRGs）。我们发现，在发育过程中，不同分化阶段的 CMs 共存。我们鉴定出一群不成熟的热稳定抗原（HSA）/分化簇 24（CD24）+CMs，它们在整个生命周期中持续存在，与其他 CM 亚群不同，它们可以在 1 周龄之前积极增殖，并在移植后植入心脏组织。在成年心脏中，出现了一群离散的 HSA/CD24+CMs，表现为单核细胞，在梗塞后频率增加。我们的工作确定了细胞表面特征，允许在所有发育阶段前瞻性分离 CMs，并在整个生命周期中检测到一小部分不成熟的 CMs，尽管频率降低，但它们对缺血刺激的激活做好了准备。这项工作为理解和治疗心脏疾病开辟了新的视角。
