近日，美国加州大学旧金山分校Benoit G. Bruneau等研究人员合作发现，分级的中胚层组装控制早期哺乳动物心脏的细胞命运和形态发生。该项研究成果发表在2023年2月2日出版的《细胞》杂志上。

通过利用改进的和可访问的计算工具，并使用全维全胚胎光片成像，研究人员在单细胞分辨率下纵向重建出早期小鼠的心脏发育。初生的中胚层祖细胞形成相反的密度和活力梯度，将原肠胚形成的时间出生顺序转换为天间隔的前外侧-后内侧排列。迁移的心前中胚层并不能严格地保持细胞间的相邻关系，空间模式只会随着新月形生心区的出现而固化。

祖细胞经历间质-上皮细胞转变，第一生心区（FHF）脊与运动心周区（JCF）相对。沿脊固定，FHF上皮细胞向前旋转JCF形成最初的心管，伴随着第二生心区的推-拉形态动力学。在未能形成新月形生心区的Mesp1突变体中，中胚层仍然高度运动但方向不连贯，导致密度梯度反转。这个活胚胎成像方法定义了心脏祖细胞的空间起源和行为，并确定了它们意想不到的形态转变。

附：英文原文

Title: Graded mesoderm assembly governs cell fate and morphogenesis of the early mammalian heart

Author: Martin H. Dominguez, Alexis Leigh Krup, Jonathon M. Muncie, Benoit G. Bruneau

Issue&Volume: 2023/02/02

Abstract: Using four-dimensional whole-embryo light sheet imaging with improved and accessiblecomputational tools, we longitudinally reconstruct early murine cardiac developmentat single-cell resolution. Nascent mesoderm progenitors form opposing density andmotility gradients, converting the temporal birth sequence of gastrulation into aspatial anterolateral-to-posteromedial arrangement. Migrating precardiac mesodermdoes not strictly preserve cellular neighbor relationships, and spatial patterns onlybecome solidified as the cardiac crescent emerges. Progenitors undergo a mesenchymal-to-epithelialtransition, with a first heart field (FHF) ridge apposing a motile juxta-cardiac field(JCF). Anchored along the ridge, the FHF epithelium rotates the JCF forward to formthe initial heart tube, along with push-pull morphodynamics of the second heart field.In Mesp1 mutants that fail to make a cardiac crescent, mesoderm remains highly motile butdirectionally incoherent, resulting in density gradient inversion. Our practicablelive embryo imaging approach defines spatial origins and behaviors of cardiac progenitorsand identifies their unanticipated morphological transitions.

DOI: 10.1016/j.cell.2023.01.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00001-6