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角蛋白19(Krt19)是心外膜细胞的一种新型标志物基因。

Keratin 19 (Krt19) is a novel marker gene for epicardial cells.

作者信息

Xu Juan, Deng Yiting, Li Guang

机构信息

Department of Cell Biology, Center for Integrative Organ Systems, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

出版信息

Front Genet. 2024 May 20;15:1385867. doi: 10.3389/fgene.2024.1385867. eCollection 2024.

Abstract

Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of specific marker genes for epicardial cells has hindered the understanding of this cell type in heart development. Through the analysis of a cardiac single cell mRNA sequencing dataset, we identified a novel epicardial gene named (). Further analysis of the expression patterns of and , a well-known epicardial gene, revealed their preferences in major cardiac cell types. Using lineage-tracing analysis, we analyzed labeled cells at multiple time windows and found that it labels epicardial cells at both embryonic and neonatal stages. Furthermore, we studied the function of epicardial cells using a diphtheria toxin A chain (DTA)-based cell ablation system. We discovered that labeled cells are essential for fetal heart development. Finally, we investigated the function of and labeled cells in neonatal mouse development. We observed that the ; mice displayed a smaller size after tamoxifen treatment, suggesting the potential importance of labeled cells in neonatal mouse development. Additionally, we found that ; mice died at early stages, likely due to defects in the kidney and spleen. In summary, we have identified as a new epicardial cell marker gene and further explored the function of epicardial cells using the and -mediated DTA ablation system.

摘要

心外膜细胞通过分泌多种生长因子并经历谱系特化成为其他心脏谱系来调节心脏生长。然而,缺乏心外膜细胞的特异性标记基因阻碍了我们对心脏发育中这种细胞类型的理解。通过对一个心脏单细胞mRNA测序数据集的分析,我们鉴定出一个名为()的新型心外膜基因。对该基因以及一个著名的心外膜基因的表达模式进行进一步分析,揭示了它们在主要心脏细胞类型中的偏好性。使用谱系追踪分析,我们在多个时间窗口分析了标记的细胞,发现它在胚胎期和新生期均标记心外膜细胞。此外,我们使用基于白喉毒素A链(DTA)的细胞消融系统研究了心外膜细胞的功能。我们发现标记的细胞对胎儿心脏发育至关重要。最后,我们研究了标记的细胞在新生小鼠发育中的功能。我们观察到;小鼠在他莫昔芬处理后体型较小,这表明标记的细胞在新生小鼠发育中可能具有重要作用。此外,我们发现;小鼠在早期死亡,可能是由于肾脏和脾脏的缺陷。总之,我们已将鉴定为一种新的心外膜细胞标记基因,并使用和介导的DTA消融系统进一步探索了心外膜细胞的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1444/11145414/9fd3ff341888/fgene-15-1385867-g001.jpg

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