eprintid: 10203574 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/20/35/74 datestamp: 2025-01-20 11:11:37 lastmod: 2025-01-20 11:11:37 status_changed: 2025-01-20 11:11:37 type: article metadata_visibility: show sword_depositor: 699 creators_name: García-Tejera, Rodrigo creators_name: Tian, Jing-Yi creators_name: Amoyel, Marc creators_name: Grima, Ramon creators_name: Schumacher, Linus J title: Licensing and niche competition in spermatogenesis: mathematical models suggest complementary regulation of tissue maintenance ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F96 keywords: Cell heterogeneity, Competition for niche access, Spermatogenesis, Stem cell licensing, Stem cells, Stochastic modelling abstract: To maintain and regenerate adult tissues after injury, division and differentiation of tissue-resident stem cells must be precisely regulated. It remains elusive which regulatory strategies prevent exhaustion or overgrowth of the stem cell pool, whether there is coordination between multiple mechanisms, and how to detect them from snapshots. In Drosophila testes, somatic stem cells transition to a state that licenses them to differentiate, but remain capable of returning to the niche and resuming cell division. Here, we build stochastic mathematical models for the somatic stem cell population to investigate how licensing contributes to homeostasis. We find that licensing, in combination with differentiation occurring in pairs, is sufficient to maintain homeostasis and prevent stem cell extinction from stochastic fluctuations. Experimental data have shown that stem cells are competing for niche access, and our mathematical models demonstrate that this contributes to the reduction in the variability of stem cell numbers but does not prevent extinction. Hence, a combination of both regulation strategies, licensing with pairwise differentiation and competition for niche access, may be needed to reduce variability and prevent extinction simultaneously. date: 2025-01 date_type: published publisher: The Company of Biologists official_url: https://doi.org/10.1242/dev.202796 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2346341 doi: 10.1242/dev.202796 medium: Print-Electronic pii: 364839 lyricists_name: Amoyel, Marc lyricists_id: MAMOY58 actors_name: Amoyel, Marc actors_id: MAMOY58 actors_role: owner funding_acknowledgements: [University of Edinburgh]; [University College London]; MR/W029219/1 [Medical Research Council]; RPG-2018-423 [Leverhulme Trust]; [College of Medicine and Veterinary Medicine, University of Edinburgh] full_text_status: public publication: Development volume: 152 number: 1 article_number: dev202796 event_location: England issn: 0950-1991 citation: García-Tejera, Rodrigo; Tian, Jing-Yi; Amoyel, Marc; Grima, Ramon; Schumacher, Linus J; (2025) Licensing and niche competition in spermatogenesis: mathematical models suggest complementary regulation of tissue maintenance. Development , 152 (1) , Article dev202796. 10.1242/dev.202796 <https://doi.org/10.1242/dev.202796>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10203574/7/Amoyel_dev202796.pdf