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Alternative direct stem cell derivatives defined by stem cell location and graded Wnt signalling

Nature Cell Biology volume 19, pages 433444 (2017) | Download Citation


Adult stem cells provide a renewable source of differentiated cells for a wide variety of tissues and generally give rise to multiple cell types. Basic principles of stem cell organization and regulation underlying this behaviour are emerging. Local niche signals maintain stem cells, while different sets of signals act outside the niche to diversify initially equivalent stem cell progeny. Here we show that Drosophila ovarian follicle stem cells (FSCs) produced two distinct cell types directly. This cell fate choice was determined by the anterior–posterior position of an FSC and by the magnitude of spatially graded Wnt pathway activity. These findings reveal a paradigm of immediate diversification of stem cell derivatives according to stem cell position within a larger population, guided by a graded niche signal. We also found that FSCs strongly resemble mammalian intestinal stem cells in many aspects of their organization, including population asymmetry and dynamic heterogeneity.

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We thank Y. Veras, R. Toueg and N. Field for technical assistance, D. Rabinowitz and H. Bussenmaker for help with statistical analyses, W. Odenwald (National Institute of Neurological Disorders and Stroke, USA), R. DasGupta (Genome Institute of Singapore, Singapore), E. Bach (New York University School of Medicine, USA), the Developmental Studies and the Bloomington Stock Center for antibodies and fly stocks, and T. Hazelrigg, M. Shen, M. Crist and J. Little for comments on the manuscript. This work was supported by the National Institutes of Health (RO1 GM079351 to D.K.); D.M. was supported in part by an NIH training grant.

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Author notes

    • Elisa Cimetta
    •  & Nina Tandon

    Present addresses: Department of Industrial Engineering (DII), Padova University, Padova 35131, Italy (E.C.); The Cooper Union for the Advancement of Science and Art, New York, New York 10003 and EpiBone, Inc., 760 Parkside Avenue, Brooklyn, New York 11226, USA (N.T.).


  1. Department of Biological Sciences, Columbia University, New York, New York 10027, USA

    • Amy Reilein
    • , David Melamed
    • , Karen Sophia Park
    • , Ari Berg
    • , Sarah Finkelstein
    •  & Daniel Kalderon
  2. Department of Biomedical Engineering, Columbia University, New York, New York 10032, USA

    • Elisa Cimetta
    • , Nina Tandon
    •  & Gordana Vunjak-Novakovic


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Conceptualization, A.R. and D.K.; methodology, A.R., E.C., N.T., G.V.-N. and D.K.; formal analysis, A.R., D.M. and D.K.; investigation, A.R., D.M., K.S.P., A.B. and S.F.; writing original draft, D.K.; writing-review and editing, A.R., D.M. and D.K.; visualization, A.R. and D.K.; funding acquisition, D.K.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Daniel Kalderon.

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  1. 1.

    (corresponding to Fig. 3a). Radial movement of FSCs.

    Maximum projections of the top 3 to 6 z-sections to show relationships of 3 presumed FSCs indicated by arrows. We included 3 to 6 z-sections in a projection in order to capture the highlighted cells throughout the imaging period despite their movement between z-sections. The projections consequently capture only one dimension of the cells’ radial movement. All cells moved regardless of radial position, but since cells in the middle z stacks principally move up and down through z stacks their movement is not captured in this compressed 2-dimensional video. The ‘white’ cell (marked by the white arrow) moved further around the germarium at 4 h 15 min and was temporarily lost from the movie. At 4 h 15 min, the ‘yellow’ cell divided; both daughters are subsequently indicated by yellow arrows. Additional presumed FSCs moved into view from the other side of the gemarium beginning at 3 h 45 min but are not indicated by arrows. At 6 h the germarium began to disintegrate as cells moved out of the posterior half. We have observed twisting rotations in germaria as they appear to attempt egg chamber budding and during these rotations cells move out of the germaria. Bar, 20 μm.

  2. 2.

    (corresponding to Fig. 3b). Radial movement of FSCs.

    Maximum projections of the top 2 or 3 z-sections to show the three cells indicated by arrows throughout the movie. The ‘white’ and ‘yellow’ cells crossed one another radially. After 3 h of imaging, cells began to move out of the germarium. Bar, 20 μm.

  3. 3.

    (corresponding to Fig. 4i). FSC movement into EC territory.

    Maximum projections of the top 2–4 z stacks are shown. The ‘white’ and ‘magenta’ cells moved anterior into Escort Cell territory. The ‘white’ and ‘red’ cells crossed paths radially at 2 h and again at 4 h.

  4. 4.

    (corresponding to Supplementary Fig. 4a). FSC movement into EC territory.

    Two labeled cells started in the 2a/b region and the ‘white’ cell moved anterior into Escort Cell territory.

  5. 5.

    (corresponding to Supplementary Fig. 4b). FSC movement into EC territory.

    Maximum projections of the top 4–6 z-sections are shown in order to include the 5 cells indicated by coloured arrows. All cells moved back and forth in radial movements and the ‘white’ cell moved anteriorly into Escort Cell territory. The ‘red’ and ‘yellow’ cells crossed radially.

  6. 6.

    (corresponding to Supplementary Fig. 4c). FSC movement into EC territory.

    Maximum projections of all z-sections are shown. Initially the ‘red’, ‘yellow’, and ‘magenta’ cells were in the top half (5 z-sections), whereas the ‘white’ cell was in the last z-section (on the other side of the germarium). The ‘magenta’ cell travelled around to the other side of the germarium. Both white and magenta cells moved anterior into Escort Cell territory.

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