Baek Seung-Han, Maiorino Enrico, Kim Hyunbum, Glass Kimberly, Raby Benjamin A, Yuan Ke
Division of Pulmonary Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Front Cardiovasc Med. 2022 Jun 1;9:876591. doi: 10.3389/fcvm.2022.876591. eCollection 2022.
Pericytes are mesenchymal-derived mural cells that wrap around capillaries and directly contact endothelial cells. Present throughout the body, including the cardiovascular system, pericytes are proposed to have multipotent cell-like properties and are involved in numerous biological processes, including regulation of vascular development, maturation, permeability, and homeostasis. Despite their physiological importance, the functional heterogeneity, differentiation process, and pathological roles of pericytes are not yet clearly understood, in part due to the inability to reliably distinguish them from other mural cell populations. Our study focused on identifying pericyte-specific markers by analyzing single-cell RNA sequencing data from tissue-specific mouse pericyte populations generated by the Tabula Muris Senis. We identified the mural cell cluster in murine lung, heart, kidney, and bladder that expressed either of two known pericyte markers, or . We further defined pericytes as those cells that co-expressed both markers within this cluster. Single-cell differential expression gene analysis compared this subset with other clusters that identified potential pericyte marker candidates, including (in the lung); (in the heart); and (in the kidney); (in the bladder); and (in lung and heart). In addition, we identified novel markers of tissue-specific pericytes and signaling pathways that may be involved in maintaining their identity. Moreover, the identified markers were further validated in Human Lung Cell Atlas and human heart single-cell RNAseq databases. Intriguingly, we found that markers of heart and lung pericytes in mice were conserved in human heart and lung pericytes. In this study, we, for the first time, identified specific pericyte markers among lung, heart, kidney, and bladder and reveal differentially expressed genes and functional relationships between mural cells.
周细胞是间充质来源的壁细胞,包裹在毛细血管周围并直接与内皮细胞接触。周细胞存在于全身,包括心血管系统,被认为具有多能细胞样特性,并参与许多生物学过程,包括血管发育、成熟、通透性和内环境稳态的调节。尽管它们在生理上很重要,但周细胞的功能异质性、分化过程和病理作用尚未完全清楚,部分原因是无法可靠地将它们与其他壁细胞群体区分开来。我们的研究重点是通过分析来自Tabula Muris Senis生成的组织特异性小鼠周细胞群体的单细胞RNA测序数据来鉴定周细胞特异性标志物。我们在小鼠肺、心脏、肾脏和膀胱中鉴定出表达两种已知周细胞标志物之一的壁细胞簇。我们进一步将周细胞定义为该簇内同时表达这两种标志物的细胞。单细胞差异表达基因分析将该亚群与其他簇进行比较,确定了潜在的周细胞标志物候选物,包括(在肺中);(在心脏中);以及(在肾脏中);(在膀胱中);以及(在肺和心脏中)。此外,我们鉴定了组织特异性周细胞的新标志物以及可能参与维持其特性的信号通路。此外,在人类肺细胞图谱和人类心脏单细胞RNA测序数据库中进一步验证了所鉴定的标志物。有趣的是,我们发现小鼠心脏和肺周细胞的标志物在人类心脏和肺周细胞中是保守的。在这项研究中,我们首次在肺、心脏、肾脏和膀胱中鉴定出特异性周细胞标志物,并揭示了壁细胞之间差异表达的基因和功能关系。