Independently paced Ca2+ oscillations in progenitor and differentiated cells in an ex vivo epithelial organ

Abstract

Cytosolic calcium is a highly dynamic, tightly regulated, and broadly conserved cellular signal. Calcium dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here we examine calcium 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 calcium oscillations after differentiation: Enteroendocrine cells exhibit single-cell calcium oscillations, while enterocytes exhibit rhythmic, long-range calcium waves. These multicellular waves do not propagate through immature progenitors (stem cells and enteroblasts), whose oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates calcium 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 calcium dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.

Epithelial Ca2+waves triggered by enteric neurons heal the gut

“…5G-H). Our findings are also supported by a recent study that detected Ca 2+ waves in R3 of the midgut 108 . Relevant to our findings cholinergic, nicotinic, Hippo, TNF pathways, as well as vagus-nerve stimulation, are being tested as therapeutics for intestinal pathologies and cancer 9,10,13,18,93,[109][110][111][112][113][114] .…”

TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila

“…Previous reports indicate that Ca 2+ oscillation within ISCs promotes their proliferation and that multiple cell types in the intestinal epithelium also have Ca 2+ oscillation ( 54 , 55 ). When we examined Ca 2+ signals in ISC/EB cell nests in 20-day-old animals, we found an almost complete loss of Ca 2+ oscillation in posterior midgut of TrpA1-KO flies, when compared with age-matched w 1118 control ( Fig.…”

Maintenance of hematopoietic stem cell niche homeostasis requires gap junction–mediated calcium signaling

“…Gap junctions (GJs) can provide a mechanism to ensure the coordination of cell signaling across large complex organs like the LG ( 13 , 27 , 28 ). GJs form channels between cells that allow the transport of nutrients, signaling molecules, and small metabolites ( 29 – 32 ).…”