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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.<\/jats:p>","DOI":"10.1242\/dev.202796","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T13:39:19Z","timestamp":1735825159000},"source":"Crossref","is-referenced-by-count":2,"title":["Licensing and niche competition in spermatogenesis: mathematical models suggest complementary regulation of tissue maintenance"],"prefix":"10.1242","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3427-3587","authenticated-orcid":false,"given":"Rodrigo","family":"Garc\u00eda-Tejera","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh 1 , Edinburgh EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Yi","family":"Tian","sequence":"additional","affiliation":[{"name":"University College London 2 Department of Cell and Developmental Biology , , London WC1E 6BT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-2097","authenticated-orcid":false,"given":"Marc","family":"Amoyel","sequence":"additional","affiliation":[{"name":"University College London 2 Department of Cell and Developmental Biology , , London WC1E 6BT ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1266-8169","authenticated-orcid":false,"given":"Ramon","family":"Grima","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Edinburgh 3 , Edinburgh EH9 3BF ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0797-3406","authenticated-orcid":false,"given":"Linus J.","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh 1 , Edinburgh EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"2025010213385777200_DEV202796C1","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.15252\/embj.201387500","article-title":"Neutral competition of stem cells is skewed by proliferative changes downstream of hh and hpo","volume":"33","author":"Amoyel","year":"2014","journal-title":"EMBO J."},{"key":"2025010213385777200_DEV202796C2","doi-asserted-by":"publisher","first-page":"3914","DOI":"10.1242\/dev.139782","article-title":"Somatic stem cell differentiation is regulated by pi3k\/tor signaling in response to local cues","volume":"143","author":"Amoyel","year":"2016","journal-title":"Development"},{"key":"2025010213385777200_DEV202796C3","doi-asserted-by":"publisher","first-page":"021116","DOI":"10.1103\/PhysRevE.81.021116","article-title":"Extinction of metastable stochastic populations","volume":"81","author":"Assaf","year":"2010","journal-title":"Phys. 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