通过心内膜前体细胞中 Sox17 表达的心内膜分化调节小鼠的心脏发育。,Scientific Reports

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通过心内膜前体细胞中 Sox17 表达的心内膜分化调节小鼠的心脏发育。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-08-16 , DOI: 10.1038/s41598-019-48321-y
Rie Saba _{1,

2} , Keiko Kitajima ₃ , Lucille Rainbow ₄ , Silvia Engert ₅ , Mami Uemura _{6,

7} , Hidekazu Ishida _{1,

8} , Ioannis Kokkinopoulos ₁ , Yasunori Shintani _{1,

9} , Shigeru Miyagawa ₁₀ , Yoshiakira Kanai ₆ , Masami Kanai-Azuma ₇ , Peter Koopman ₁₁ , Chikara Meno ₃ , John Kenny _{4,

12} , Heiko Lickert ₅ , Yumiko Saga ₁₃ , Ken Suzuki ₁ , Yoshiki Sawa ₁₀ , Kenta Yashiro _{1,

2,

10,

14}

Affiliation

Centres for Microvascular Research and for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Cardiac Regeneration and Therapeutics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Developmental Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.
Department of Veterinary Anatomy, The University of Tokyo, Tokyo, Japan.
Department of Experimental Animal Models for Human Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Teagasc Food Research Centre, Moorepark, Co Cork, Ireland.
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Shizuoka, Japan.
Division of Anatomy and Developmental Biology, Department of Anatomy, Kyoto Prefectural University of Medicine, Kyoto, Japan.

心内膜是脊椎动物心脏的内皮成分，在心脏发育中起着关键作用。然而，在胚胎发生过程中，心内膜在何处、何时以及如何分离在很大程度上仍然未知。我们现在显示从胚胎日 (E) 7.5 到 E8.5 表达 Sry 型 HMG 盒基因 Sox17 的 Nkx2-5+ 心脏祖细胞 (CPC) 特异性分化为小鼠胚胎的心内膜。尽管 Sox17 对心内膜的命运不是必需的或不充分的，但它可以使 CPC 的命运偏向于心内膜。另一方面，心脏发育需要心内膜中的 Sox17 表达。中胚层中 Sox17 的缺失显着损害了心内膜的细胞增殖和行为发育。心肌细胞增殖、心室小梁、在 Sox17 突变体中，心肌增厚也以非细胞自主方式受损，这可能是由于 NOTCH 信号传导下调所致。一个未知信号，由 Sox17 调节，是培养心肌所必需的，它是突变胚胎中 NOTCH 相关基因减少的原因。因此，我们的结果提供了对心内膜分化及其在心脏发育中的作用的深入了解。

"点击查看英文标题和摘要"

Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice.

The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5+ cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5 to E8.5 specifically differentiate into the endocardium in mouse embryos. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cell-autonomous manner in the Sox17 mutant, likely as a consequence of down-regulation of NOTCH signaling. An unknown signal, regulated by Sox17 and required for nurturing of the myocardium, is responsible for the reduction in NOTCH-related genes in the mutant embryos. Our results thus provide insight into differentiation of the endocardium and its role in heart development.

更新日期：2019-08-16

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