Live Imaging of the Drosophila Spermatogonial Stem Cell Niche Reveals Novel Mechanisms Regulating Germline Stem Cell Output

Overview

Journal Development

Specialty Biology

Date 2011 Jul 15

PMID 21752931

Citations 84

Authors

X Rebecca Sheng

Erika Matunis

Affiliations

Soon will be listed here.

Abstract

Adult stem cells modulate their output by varying between symmetric and asymmetric divisions, but have rarely been observed in living intact tissues. Germline stem cells (GSCs) in the Drosophila testis are anchored to somatic hub cells and were thought to exclusively undergo oriented asymmetric divisions, producing one stem cell that remains hub-anchored and one daughter cell displaced out of the stem cell-maintaining micro-environment (niche). We developed extended live imaging of the Drosophila testis niche, allowing us to track individual germline cells. Surprisingly, new wild-type GSCs are generated in the niche during steady-state tissue maintenance by a previously undetected event we term 'symmetric renewal', where interconnected GSC-daughter cell pairs swivel such that both cells contact the hub. We also captured GSCs undergoing direct differentiation by detaching from the hub. Following starvation-induced GSC loss, GSC numbers are restored by symmetric renewals. Furthermore, upon more severe (genetically induced) GSC loss, both symmetric renewal and de-differentiation (where interconnected spermatogonia fragment into pairs while moving towards then establishing contact with the hub) occur simultaneously to replenish the GSC pool. Thus, stereotypically oriented stem cell divisions are not always correlated with an asymmetric outcome in cell fate, and changes in stem cell output are governed by altered signals in response to tissue requirements.

Citing Articles

Increased levels of lagging strand polymerase α in an adult stem cell lineage affect replication-coupled histone incorporation.

Davis B, Snedeker J, Ranjan R, Wooten M, Barton S, Blundon J Sci Adv. 2025; 11(9):eadu6799.

PMID: 40020063 PMC: 11870066. DOI: 10.1126/sciadv.adu6799.

Maintenance of niche architecture requires actomyosin and enables proper stem cell signaling and oriented division in the Drosophila testis.

Vida G, Botto E, DiNardo S Development. 2024; 152(1).

PMID: 39620974 PMC: 11795290. DOI: 10.1242/dev.204498.

Unusual modes of cell and nuclear divisions characterise Drosophila development.

Yang Q, Wijaya F, Kapoor R, Chandrasekaran H, Jagtiani S, Moran I Biochem Soc Trans. 2024; 52(6):2281-2295.

PMID: 39508395 PMC: 11668308. DOI: 10.1042/BST20231341.

Mechanisms of Germline Stem Cell Competition across Species.

Hodge R, Bach E Life (Basel). 2024; 14(10).

PMID: 39459551 PMC: 11509876. DOI: 10.3390/life14101251.

Modulating DNA Polα Enhances Cell Reprogramming Across Species.

Ranjan R, Ma B, Gleason R, Liao Y, Bi Y, Davis B bioRxiv. 2024; .

PMID: 39345551 PMC: 11429986. DOI: 10.1101/2024.09.19.613993.

References

Morrison S, Spradling A . Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008; 132(4):598-611. PMC: 4505728. DOI: 10.1016/j.cell.2008.01.038. View

Wang Z, Lin H . The division of Drosophila germline stem cells and their precursors requires a specific cyclin. Curr Biol. 2005; 15(4):328-33. DOI: 10.1016/j.cub.2005.02.016. 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

Read R, Bach E, Cagan R . Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways. Mol Cell Biol. 2004; 24(15):6676-89. PMC: 444864. DOI: 10.1128/MCB.24.15.6676-6689.2004. View

Issigonis M, Tulina N, de Cuevas M, Brawley C, Sandler L, Matunis E . JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche. Science. 2009; 326(5949):153-6. PMC: 3073347. DOI: 10.1126/science.1176817. View

Shivdasani A, Ingham P . Regulation of stem cell maintenance and transit amplifying cell proliferation by tgf-beta signaling in Drosophila spermatogenesis. Curr Biol. 2003; 13(23):2065-72. DOI: 10.1016/j.cub.2003.10.063. View

Prasad M, Jang A, Starz-Gaiano M, Melani M, Montell D . A protocol for culturing Drosophila melanogaster stage 9 egg chambers for live imaging. Nat Protoc. 2007; 2(10):2467-73. DOI: 10.1038/nprot.2007.363. View

Lo Celso C, Fleming H, Wu J, Zhao C, Miake-Lye S, Fujisaki J . Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2008; 457(7225):92-6. PMC: 2820276. DOI: 10.1038/nature07434. View

Doupe D, Klein A, Simons B, Jones P . The ordered architecture of murine ear epidermis is maintained by progenitor cells with random fate. Dev Cell. 2010; 18(2):317-23. DOI: 10.1016/j.devcel.2009.12.016. View

10.

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

11.

Yamashita Y, Yuan H, Cheng J, Hunt A . Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol. 2010; 2(1):a001313. PMC: 2827902. DOI: 10.1101/cshperspect.a001313. View

12.

Yoshida S, Sukeno M, Nabeshima Y . A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science. 2007; 317(5845):1722-6. DOI: 10.1126/science.1144885. View

13.

Nakagawa T, Sharma M, Nabeshima Y, Braun R, Yoshida S . Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment. Science. 2010; 328(5974):62-7. PMC: 2981100. DOI: 10.1126/science.1182868. View

14.

Rossi D, Jamieson C, Weissman I . Stems cells and the pathways to aging and cancer. Cell. 2008; 132(4):681-96. DOI: 10.1016/j.cell.2008.01.036. View

15.

Ohlstein B, McKearin D . Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells. Development. 1997; 124(18):3651-62. DOI: 10.1242/dev.124.18.3651. View

16.

Johansen K, Iwaki D, Lengyel J . Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium. Development. 2002; 130(1):135-45. DOI: 10.1242/dev.00202. View

17.

Nakagawa T, Nabeshima Y, Yoshida S . Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Dev Cell. 2007; 12(2):195-206. DOI: 10.1016/j.devcel.2007.01.002. View

18.

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

19.

Carpenter A . EM autoradiographic evidence that DNA synthesis occurs at recombination nodules during meiosis in Drosophila melanogaster females. Chromosoma. 1981; 83(1):59-80. DOI: 10.1007/BF00286016. View

20.

Singh A, Dalton S . The cell cycle and Myc intersect with mechanisms that regulate pluripotency and reprogramming. Cell Stem Cell. 2009; 5(2):141-9. PMC: 2909475. DOI: 10.1016/j.stem.2009.07.003. View