Sox7-positive endothelial progenitors establish coronary arteries and govern ventricular compaction.
Sox7-positive endothelial progenitors establish coronary arteries and govern ventricular compaction.
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DOI：
10.15252/embr.202255043
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发表时间：
2023-10-09
期刊：
影响因子：
7.7
通讯作者：
中科院分区：
文献类型：
--
作者：
心脏内皮通过协调小梁形成和致密化影响心室腔的发育。然而，介导这种协调的内皮特异性分子机制尚未完全了解。在这里，我们确定了Sox 7转录因子作为一个重要的线索，指示心室腔发育过程中的心脏内皮细胞的身份。小鼠中内皮特异性Sox 7功能丧失导致类似于非致密化心肌病的心室缺陷，突变心脏中小梁和致密心肌细胞的比例发生变化。这种表型被异常冠状动脉形成所掩盖。Sox 7功能的丧失破坏了Notch途径和连接蛋白37和40的转录调节，这些连接蛋白控制冠状动脉特化。在Sox 7内皮特异性缺失后，单核转录组学分析鉴定了Sox 9/Gpc 3阳性内皮祖细胞亚群的耗竭和髓样细胞谱系的增加。命运图谱分析显示，Sox 7缺失的内皮细胞亚群转分化为造血细胞而不是心肌细胞谱系。我们的研究结果确定Sox 7维持心脏内皮细胞的身份，这对驱动心室致密化和冠状动脉发育的细胞串扰至关重要。Sox 7主要通过调节冠状动脉形成和指导心室致密化而对内皮和内皮细胞分化至关重要。
The cardiac endothelium influences ventricular chamber development by coordinating trabeculation and compaction. However, the endothelial‐specific molecular mechanisms mediating this coordination are not fully understood. Here, we identify the Sox7 transcription factor as a critical cue instructing cardiac endothelium identity during ventricular chamber development. Endothelial‐specific loss of Sox7 function in mice results in cardiac ventricular defects similar to non‐compaction cardiomyopathy, with a change in the proportions of trabecular and compact cardiomyocytes in the mutant hearts. This phenotype is paralleled by abnormal coronary artery formation. Loss of Sox7 function disrupts the transcriptional regulation of the Notch pathway and connexins 37 and 40, which govern coronary arterial specification. Upon Sox7 endothelial‐specific deletion, single‐nuclei transcriptomics analysis identifies the depletion of a subset of Sox9/Gpc3‐positive endocardial progenitor cells and an increase in erythro‐myeloid cell lineages. Fate mapping analysis reveals that a subset of Sox7‐null endothelial cells transdifferentiate into hematopoietic but not cardiomyocyte lineages. Our findings determine that Sox7 maintains cardiac endothelial cell identity, which is crucial to the cellular cross‐talk that drives ventricular compaction and coronary artery development. Sox7 is essential for endothelial and endocardial differentiation mostly via the modulation of coronary arteries formation and the instruction of cardiac ventricular compaction.
影响因子：
2.7
作者：
Afouda BA;Lynch AT;de Paiva Alves E;Hoppler S
通讯作者：
Hoppler S
影响因子：
3.8
作者：
Hoang P;Huebsch N;Bang SH;Siemons BA;Conklin BR;Healy KE;Ma Z;Jacquir S
通讯作者：
Jacquir S
影响因子：
2.9
作者：
Nelson, Timothy J.;Chiriac, Anca;Faustino, Randolph S.;Crespo-Diaz, Ruben J.;Behfar, Atta;Terzic, Andre
通讯作者：
Terzic, Andre