Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Departments of Mechanical Engineering and Biomolecular Science and Engineering, University of California, Santa Barbara, CA 93106, USA.
J Cell Sci. 2022 Jul 15;135(14). doi: 10.1242/jcs.260249. Epub 2022 Jul 19.
Cytosolic Ca2+ is a highly dynamic, tightly regulated and broadly conserved cellular signal. Ca2+ dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here, we examine Ca2+ dynamics in the adult Drosophila intestine, a self-renewing epithelial organ in which stem cells continuously produce daughters that differentiate into either enteroendocrine cells or enterocytes. Live imaging of whole organs ex vivo reveals that stem-cell daughters adopt strikingly distinct patterns of Ca2+ oscillations after differentiation: enteroendocrine cells exhibit single-cell Ca2+ oscillations, whereas enterocytes exhibit rhythmic, long-range Ca2+ waves. These multicellular waves do not propagate through immature progenitors (stem cells and enteroblasts), of which the oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates Ca2+ oscillations in all cell types - even, intriguingly, in progenitor and enteroendocrine cells that are surrounded only by enterocytes. Our findings establish that cells adopt fate-specific modes of Ca2+ dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.
细胞质中的 Ca2+ 是一种高度动态、严格调节和广泛保守的细胞信号。Ca2+ 动力学在细胞的单细胞培养中已经得到了广泛的研究，然而，体内的器官由干细胞和分化细胞组成的异质群体组成。在这里，我们研究了成年果蝇肠道中的 Ca2+ 动力学，这是一个自我更新的上皮器官，其中干细胞不断产生分化为肠内分泌细胞或肠细胞的女儿细胞。对整个器官的活体成像显示，分化后的干细胞女儿细胞表现出明显不同的 Ca2+ 振荡模式：肠内分泌细胞表现出单细胞 Ca2+ 振荡，而肠细胞表现出节律性的长程 Ca2+ 波。这些多细胞波不会通过不成熟的祖细胞（干细胞和肠母细胞）传播，其振荡频率大约是肠内分泌细胞的一半。器官级别的间隙连接抑制消除了所有细胞类型的 Ca2+ 振荡——甚至在仅被肠细胞包围的祖细胞和肠内分泌细胞中也是如此。我们的发现确立了细胞在终末分化时采用特定命运的 Ca2+ 动力学模式，并揭示了单个、连贯的上皮组织中不同细胞类型的振荡动力学是独立调节的。
