Pogontke C, Guadix J A, Sánchez-Tévar A M, Muñoz-Chápuli R, Ruiz-Villalba A, Pérez-Pomares J M
Department of Animal Biology, Faculty of Sciences, University of Málaga, Málaga, Spain.
Instituto Malagueño de Biomedicina (IBIMA)-Plataforma BIONAND, Universidad de Málaga, Málaga, Spain.
Front Cell Dev Biol. 2022 May 30;10:864765. doi: 10.3389/fcell.2022.864765. eCollection 2022.
The cardiac interstitial cellular fraction is composed of multiple cell types. Some of these cells are known to express some well-known stem cell markers such as c-Kit and Sca1, but they are no longer accepted to be true cardiac stem cells. Although their existence in the cardiac interstitium has not been disputed, their dynamic throughout development, specific embryonic origin, and potential heterogeneity remain unknown. In this study, we hypothesized that both c-Kit and Sca1 cardiac interstitial cell (CIC) subpopulations are related to the Wilms' tumor 1 (Wt1) epicardial lineage. In this study, we have used genetic cell lineage tracing methods, immunohistochemistry, and FACS techniques to characterize cardiac c-Kit and Sca1 cells. Our data show that approximately 50% of cardiac c-Kit cells are derived from the Wt1-lineage at E15.5. This subpopulation decreased along with embryonic development, disappearing from P7 onwards. We found that a large proportion of cardiac c-Kit cells express specific markers strongly suggesting they are blood-borne cells. On the contrary, the percentage of Sca1 cells within the Wt1-lineage increases postnatally. In accordance with these findings, 90% of adult epicardial-derived endothelial cells and 60% of mEFSK4 cardiac fibroblasts expressed Sca1. Our study revealed a minor contribution of the Wt1-epicardial lineage to c-Kit CIC from embryonic stages to adulthood. Remarkably, a major part of the adult epicardial-derived cell fraction is enriched in Sca1, suggesting that this subpopulation of CICs is heterogeneous from their embryonic origin. The study of this heterogeneity can be instrumental to the development of diagnostic and prognostic tests for the evaluation of cardiac homeostasis and cardiac interstitium response to pathologic stimuli.
心脏间质细胞部分由多种细胞类型组成。已知其中一些细胞表达一些著名的干细胞标志物，如c-Kit和Sca1，但它们不再被认为是真正的心脏干细胞。尽管它们在心脏间质中的存在没有争议，但其在整个发育过程中的动态变化、特定的胚胎起源和潜在的异质性仍然未知。在本研究中，我们假设c-Kit和Sca1心脏间质细胞（CIC）亚群均与威尔姆斯瘤1（Wt1）心外膜谱系相关。在本研究中，我们使用了遗传细胞谱系追踪方法、免疫组织化学和FACS技术来表征心脏c-Kit和Sca1细胞。我们的数据表明，在E15.5时，约50%的心脏c-Kit细胞源自Wt1谱系。这一亚群随着胚胎发育而减少，从P7开始消失。我们发现，很大一部分心脏c-Kit细胞强烈表达特定标志物，强烈表明它们是血源性细胞。相反，Wt1谱系内Sca1细胞的百分比在出生后增加。根据这些发现，90%的成年心外膜来源的内皮细胞和60%的mEFSK4心脏成纤维细胞表达Sca1。我们的研究揭示了从胚胎期到成年期，Wt1心外膜谱系对c-Kit CIC的贡献较小。值得注意的是，成年心外膜来源的细胞部分主要富集在Sca1中，这表明这一CIC亚群从胚胎起源就具有异质性。对这种异质性的研究有助于开发用于评估心脏内环境稳态和心脏间质对病理刺激反应的诊断和预后测试。
