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线粒体ATP模式预测组织折叠。

Patterns of Mitochondrial ATP Predict Tissue Folding.

作者信息

Lemma Bezia, Rothstein Megan, Zhang Pengfei, Waas Bridget, Kilwein Marcus, Topiwala Safiya, Zhang Sherry X, Sudhakar Anvitha, Goodwin Katharine, Gavis Elizabeth R, Mallarino Ricardo, Kosmrlj Andrej, Nelson Celeste M

机构信息

Departments of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

出版信息

bioRxiv. 2025 Aug 31:2025.08.31.673364. doi: 10.1101/2025.08.31.673364.

Abstract

The construction of complex tissue shapes during embryonic development results from spatial patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during morphogenesis. Specifically, mitochondria are locally enriched at the apical sides of epithelial cells during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Timelapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase in epithelial cells prior to actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apicobasal patterning are conserved during apical constriction in flies, chicks, and mice, and these subcellular patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in embryonic development.

摘要

胚胎发育过程中复杂组织形态的构建源于基因表达的空间模式以及由ATP水解产生的化学能驱动的机械力。我们发现,在形态发生过程中化学能也呈现出类似的模式。具体而言,在顶端收缩过程中,线粒体在上皮细胞的顶端侧局部富集,顶端收缩在动物界广泛用于折叠上皮组织。延时成像、空间转录组学以及氧消耗率测量结果表明,在肌动球蛋白收缩和组织折叠之前,上皮细胞中的线粒体密度、电位和ATP增加,而抑制氧化磷酸化可阻止这种增加。果蝇、小鸡和小鼠在顶端收缩过程中线粒体富集和顶基模式是保守的,这些亚细胞模式可用于通过计算预测组织折叠模式。这些发现突出了胚胎发育中生物能量学的空间维度。

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