Topological defects control collective dynamics in neural progenitor cell cultures
Topological defects control collective dynamics in neural progenitor cell cultures
复制标题
DOI：
10.1038/nature22321
复制
发表时间：
2017-05-18
期刊：
影响因子：
64.8
通讯作者：
Sano, Masaki
中科院分区：
文献类型：
--
作者：
Kawaguchi, Kyogo;Kageyama, Ryoichiro;Sano, Masaki
培养的干细胞不仅成为再生医学和发育生物学的标准平台，而且也成为生物物理学研究的标准平台。然而，培养的干细胞在形态和细胞间相互作用产生的宏观模式方面的特征在很大程度上仍然是定性的。在这里，我们报道了培养的小鼠神经前体细胞(NPC)的集体动力学，它是在中枢神经系统中产生细胞的多潜能干细胞(1)。在低密度时，NPC以阿米巴虫一样的方式随机移动。然而，高密度的NPC拉长并彼此对齐它们的形状，以相对较高的速度滑动。尽管单个细胞的运动方向沿着排列轴线随机颠倒，但这些细胞能够形成一种排列到长度尺度的图案，类似于在成人大脑中观察到的迁移流(2)。培养物内的二维排列顺序显示包含穿插的拓扑缺陷的液晶图案，其缠绕数为+1/2和-1/2(由于细胞间相互作用的头-尾对称产生的向列型特征，半整数)。我们发现细胞在+1/2缺陷处快速堆积，并形成三维土丘。缺陷周围单细胞水平的成像使我们能够量化速度场和演变的细胞密度；细胞不仅集中在+1/2缺陷处，而且还逃脱了-1/2缺陷。我们提出了缺陷周围晶胞密度不稳定的一般机制，这种不稳定是由于各向异性摩擦和有源力场之间的相互作用引起的。
Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system(1). At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain(2). The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and -1/2 (half-integer due to the nematic feature that arises from the head-tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from -1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.