Neutral Competition of Stem Cells is Skewed by Proliferative Changes Downstream of Hh and Hpo

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Aug 6

PMID 25092766

Citations 47

Authors

Marc Amoyel

Benjamin D Simons

Erika A Bach

Affiliations

Soon will be listed here.

Abstract

Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process.

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References

Pan D . The hippo signaling pathway in development and cancer. Dev Cell. 2010; 19(4):491-505. PMC: 3124840. DOI: 10.1016/j.devcel.2010.09.011. View

Tanentzapf G, Brown N . An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton. Nat Cell Biol. 2006; 8(6):601-6. DOI: 10.1038/ncb1411. View

Snippert H, van der Flier L, Sato T, van Es J, van den Born M, Kroon-Veenboer C . Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell. 2010; 143(1):134-44. DOI: 10.1016/j.cell.2010.09.016. View

Wang L, Li Z, Cai Y . The JAK/STAT pathway positively regulates DPP signaling in the Drosophila germline stem cell niche. J Cell Biol. 2008; 180(4):721-8. PMC: 2265565. DOI: 10.1083/jcb.200711022. View

Ritsma L, Ellenbroek S, Zomer A, Snippert H, de Sauvage F, Simons B . Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature. 2014; 507(7492):362-365. PMC: 3964820. DOI: 10.1038/nature12972. View

Wallenfang M, Nayak R, DiNardo S . Dynamics of the male germline stem cell population during aging of Drosophila melanogaster. Aging Cell. 2006; 5(4):297-304. DOI: 10.1111/j.1474-9726.2006.00221.x. View

Tanentzapf G, Devenport D, Godt D, Brown N . Integrin-dependent anchoring of a stem-cell niche. Nat Cell Biol. 2007; 9(12):1413-8. PMC: 3529653. DOI: 10.1038/ncb1660. View

Potter C, Huang H, Xu T . Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001; 105(3):357-68. DOI: 10.1016/s0092-8674(01)00333-6. View

Lopez-Garcia C, Klein A, Simons B, Winton D . Intestinal stem cell replacement follows a pattern of neutral drift. Science. 2010; 330(6005):822-5. DOI: 10.1126/science.1196236. View

10.

Inaba M, Yuan H, Yamashita Y . String (Cdc25) regulates stem cell maintenance, proliferation and aging in Drosophila testis. Development. 2011; 138(23):5079-86. PMC: 3210491. DOI: 10.1242/dev.072579. View

11.

Doupe D, Alcolea M, Roshan A, Zhang G, Klein A, Simons B . A single progenitor population switches behavior to maintain and repair esophageal epithelium. Science. 2012; 337(6098):1091-3. PMC: 3527005. DOI: 10.1126/science.1218835. View

12.

Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C . The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol. 2005; 8(1):27-36. DOI: 10.1038/ncb1339. View

13.

Lee T, Luo L . Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999; 22(3):451-61. DOI: 10.1016/s0896-6273(00)80701-1. View

14.

de Cuevas M, Matunis E . The stem cell niche: lessons from the Drosophila testis. Development. 2011; 138(14):2861-9. PMC: 3119301. DOI: 10.1242/dev.056242. View

15.

Yamashita Y, Mahowald A, Perlin J, Fuller M . Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science. 2007; 315(5811):518-21. PMC: 2563045. DOI: 10.1126/science.1134910. View

16.

Vanharanta S, Massague J . Field cancerization: something new under the sun. Cell. 2012; 149(6):1179-81. DOI: 10.1016/j.cell.2012.05.013. View

17.

Flaherty M, Salis P, Evans C, Ekas L, Marouf A, Zavadil J . chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. Dev Cell. 2010; 18(4):556-68. PMC: 2859208. DOI: 10.1016/j.devcel.2010.02.006. View

18.

DiNardo S, Okegbe T, Wingert L, Freilich S, Terry N . lines and bowl affect the specification of cyst stem cells and niche cells in the Drosophila testis. Development. 2011; 138(9):1687-96. PMC: 3074445. DOI: 10.1242/dev.057364. View

19.

Price M, Kalderon D . Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A. Development. 1999; 126(19):4331-9. DOI: 10.1242/dev.126.19.4331. View

20.

Moreno E, Basler K . dMyc transforms cells into super-competitors. Cell. 2004; 117(1):117-29. DOI: 10.1016/s0092-8674(04)00262-4. View