小柯机器人

张力异质性决定细胞命运
2020-11-20 13:58

德国马克斯·普朗克心肺研究所Didier Y. R. Stainier和Rashmi Priya课题组合作取得最新进展。他们提出张力异质性指导形态和命运来塑造心肌壁。2020年11月18日出版的《自然》杂志发表了这项成果。

他们显示局部张力异质性驱动斑马鱼心脏小梁形成过程中的器官尺度模式和细胞命运决定。增殖诱导的细胞在组织尺度上的拥挤触发了致密层心肌细胞之间的张力异质性,并驱使那些具有较高收缩能力的细胞脱层,并植入小梁层。实验上,致密层心肌细胞内的拥挤增加可增加分层,而减少则可消除分层。通过在缺乏小梁的斑马鱼模型中使用基因镶嵌,即在没有关键上游信号(例如Nrg-Erbb2或血流)的情况下,他们发现诱导肌动球蛋白的收缩可以挽救心肌细胞的分层,并足以驱动心肌细胞的命运规范。Notch报告子在致密层心肌细胞中的表达。

此外,Notch信号干扰了心肌细胞中的放线菌素机制,以限制过度分层,从而保留了心肌壁的结构。因此,组织尺度的力会聚在局部细胞器上,以产生复杂的形式并调节细胞命运的选择,并且这些多尺度的调节相互作用确保了强大的自组织器官模式。

研究人员表示,尚不清楚如何出现各种细胞命运和复杂形式并相互反馈以塑造功能器官。在发育中的心脏,心肌从简单的上皮过渡到复杂的组织,该组织由不同的层组成:外部紧密层和内部小梁层。此过程中的缺陷(称为心脏小梁)会引起心肌病和胚胎致死性,但如何打破组织对称性来特化小梁型心肌细胞尚不清楚。

附:英文原文

Title: Tension heterogeneity directs form and fate to pattern the myocardial wall

Author: Rashmi Priya, Srinivas Allanki, Alessandra Gentile, Shivani Mansingh, Veronica Uribe, Hans-Martin Maischein, Didier Y. R. Stainier

Issue&Volume: 2020-11-18

Abstract: How diverse cell fates and complex forms emerge and feed back to each other to sculpt functional organs remains unclear. In the developing heart, the myocardium transitions from a simple epithelium to an intricate tissue that consists of distinct layers: the outer compact and inner trabecular layers. Defects in this process, which is known as cardiac trabeculation, cause cardiomyopathies and embryonic lethality, yet how tissue symmetry is broken to specify trabecular cardiomyocytes is unknown. Here we show that local tension heterogeneity drives organ-scale patterning and cell-fate decisions during cardiac trabeculation in zebrafish. Proliferation-induced cellular crowding at the tissue scale triggers tension heterogeneity among cardiomyocytes of the compact layer and drives those with higher contractility to delaminate and seed the trabecular layer. Experimentally, increasing crowding within the compact layer cardiomyocytes augments delamination, whereas decreasing it abrogates delamination. Using genetic mosaics in trabeculation-deficient zebrafish models—that is, in the absence of critical upstream signals such as Nrg–Erbb2 or blood flow—we find that inducing actomyosin contractility rescues cardiomyocyte delamination and is sufficient to drive cardiomyocyte fate specification, as assessed by Notch reporter expression in compact layer cardiomyocytes. Furthermore, Notch signalling perturbs the actomyosin machinery in cardiomyocytes to restrict excessive delamination, thereby preserving the architecture of the myocardial wall. Thus, tissue-scale forces converge on local cellular mechanics to generate complex forms and modulate cell-fate choices, and these multiscale regulatory interactions ensure robust self-organized organ patterning.

DOI: 10.1038/s41586-020-2946-9

Source: https://www.nature.com/articles/s41586-020-2946-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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