張力異質性決定細胞命運
作者：
小柯機器人發布時間：2020/11/20 13:58:26
德國馬克斯·普朗克心肺研究所Didier Y. R. Stainier和Rashmi Priya課題組合作取得最新進展。他們提出張力異質性指導形態和命運來塑造心肌壁。2020年11月18日出版的《自然》雜誌發表了這項成果。
他們顯示局部張力異質性驅動斑馬魚心臟小梁形成過程中的器官尺度模式和細胞命運決定。增殖誘導的細胞在組織尺度上的擁擠觸發了緻密層心肌細胞之間的張力異質性，並驅使那些具有較高收縮能力的細胞脫層，並植入小梁層。實驗上，緻密層心肌細胞內的擁擠增加可增加分層，而減少則可消除分層。通過在缺乏小梁的斑馬魚模型中使用基因鑲嵌，即在沒有關鍵上遊信號（例如Nrg-Erbb2或血流）的情況下，他們發現誘導肌動球蛋白的收縮可以挽救心肌細胞的分層，並足以驅動心肌細胞的命運規範。Notch報告子在緻密層心肌細胞中的表達。
此外，Notch信號幹擾了心肌細胞中的放線菌素機制，以限制過度分層，從而保留了心肌壁的結構。因此，組織尺度的力會聚在局部細胞器上，以產生複雜的形式並調節細胞命運的選擇，並且這些多尺度的調節相互作用確保了強大的自組織器官模式。
研究人員表示，尚不清楚如何出現各種細胞命運和複雜形式並相互反饋以塑造功能器官。在發育中的心臟，心肌從簡單的上皮過渡到複雜的組織，該組織由不同的層組成：外部緊密層和內部小梁層。此過程中的缺陷（稱為心臟小梁）會引起心肌病和胚胎致死性，但如何打破組織對稱性來特化小梁型心肌細胞尚不清楚。
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