心臓のコミュニティ(Communities of the Heart)

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2024-03-13 カリフォルニア大学サンディエゴ校(UCSD)

エリー・ファラ氏らの研究によれば、心臓の細胞は成人後に再生しないが、洗練された生化学的コミュニケーションを行う。心臓の正確な構造形成が重要で、不正確な場合は先天性心疾患や成人の心臓疾患が引き起こされる。そのため、心臓細胞のコミュニケーションを理解することは重要であり、この研究はその理解を深め、新しい診断法や治療法の開発に役立つ可能性がある。

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発達中のヒト心臓を形成する空間的に組織化された細胞コミュニティ Spatially organized cellular communities form the developing human heart

Elie N. Farah,Robert K. Hu,Colin Kern,Qingquan Zhang,Ting-Yu Lu,Qixuan Ma,Shaina Tran,Bo Zhang,Daniel Carlin,Alexander Monell,Andrew P. Blair,Zilu Wang,Jacqueline Eschbach,Bin Li,Eugin Destici,Bing Ren,Sylvia M. Evans,Shaochen Chen,Quan Zhu & Neil C. Chi
Nature  Published:13 March 2024
DOI:https://doi.org/10.1038/s41586-024-07171-z

心臓のコミュニティ(Communities of the Heart)

Abstract

The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell–cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.

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