{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:47:02Z","timestamp":1787878022286,"version":"build-2784847793"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pituitary gland contains SOX2-expressing stem cells. However, their functional significance remains largely unmapped. We investigated their importance by depleting SOX2<jats:sup>+<\/jats:sup> cells through diphtheria toxin (DT)-mediated ablation. DT treatment of adult Sox2<jats:sup>CreERT2\/+<\/jats:sup>;R26<jats:sup>iDTR\/+<\/jats:sup> mice (after tamoxifen-induced expression of DT receptor in SOX2<jats:sup>+<\/jats:sup> cells) resulted in 80% obliteration of SOX2<jats:sup>+<\/jats:sup> cells in the endocrine pituitary, coinciding with reduced pituisphere-forming activity. Counterintuitively for a stem cell population, the SOX2<jats:sup>+<\/jats:sup> cell compartment did not repopulate. Considering the more active phenotype of the stem cells during early-postnatal pituitary maturation, SOX2<jats:sup>+<\/jats:sup> cell ablation was also performed in 4- and 1-week-old animals. Ablation grade diminished with decreasing age and was accompanied by a proliferative reaction of the SOX2<jats:sup>+<\/jats:sup> cells, suggesting a rescue attempt. Despite this activation, SOX2<jats:sup>+<\/jats:sup> cells did also not recover. Finally, the major SOX2<jats:sup>+<\/jats:sup> cell depletion in adult mice did not affect the homeostatic maintenance of pituitary hormonal cell populations, nor the corticotrope remodelling response to adrenalectomy challenge. Taken together, our study shows that pituitary SOX2<jats:sup>+<\/jats:sup> fail to regenerate after major depletion which does not affect adult endocrine cell homeostasis and remodelling. Thus, pituitary SOX2<jats:sup>+<\/jats:sup> cells may constitute a copious stem cell reserve or may have other critical role(s) still to be clearly defined.<\/jats:p>","DOI":"10.1038\/s41598-017-16796-2","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T10:28:07Z","timestamp":1511951287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Major depletion of SOX2+ stem cells in the adult pituitary is not restored which does not affect hormonal cell homeostasis and remodelling"],"prefix":"10.1038","volume":"7","author":[{"given":"Heleen","family":"Roose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Boretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny","family":"Gysemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Vennekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vankelecom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"16796_CR1","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.ygcen.2009.11.007","volume":"166","author":"H Vankelecom","year":"2010","unstructured":"Vankelecom, H. & Gremeaux, L. Stem cells in the pituitary gland: A burgeoning field. Gen. Comp. Endocrinol. \n                           166, 478\u2013488 (2010).","journal-title":"Gen. Comp. Endocrinol."},{"key":"16796_CR2","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1073\/pnas.0707886105","volume":"105","author":"T Fauquier","year":"2008","unstructured":"Fauquier, T., Rizzoti, K., Dattani, M., Lovell-Badge, R. & Robinson, I. C. A. F. SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland. Proc. Natl. Acad. Sci. USA \n                           105, 2907\u20132912 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"16796_CR3","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1002\/stem.51","volume":"27","author":"J Chen","year":"2009","unstructured":"Chen, J. et al. Pituitary progenitor cells tracked down by side population dissection. Stem Cells \n                           27, 1182\u20131195 (2009).","journal-title":"Stem Cells"},{"key":"16796_CR4","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.stem.2011.09.001","volume":"9","author":"K Arnold","year":"2011","unstructured":"Arnold, K. et al. Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell \n                           9, 317\u2013329 (2011).","journal-title":"Cell Stem Cell"},{"key":"16796_CR5","first-page":"15","volume":"12","author":"A Sarkar","year":"2013","unstructured":"Sarkar, A. & Hochedlinger, K. The Sox family of transcription factors\u202f: versatile regulators of stem and progenitor cell fate. Stem. Cell \n                           12, 15\u201330 (2013).","journal-title":"Cell"},{"key":"16796_CR6","doi-asserted-by":"publisher","first-page":"3245","DOI":"10.1089\/scd.2012.0290","volume":"21","author":"Q Fu","year":"2012","unstructured":"Fu, Q. & Vankelecom, H. Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation. Stem Cells Dev. \n                           21, 3245\u20133257 (2012).","journal-title":"Stem Cells Dev."},{"key":"16796_CR7","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1210\/en.2012-1152","volume":"153","author":"Q Fu","year":"2012","unstructured":"Fu, Q. et al. The adult pituitary shows stem\/progenitor cell activation in response to injury and is capable of regeneration. Endocrinology \n                           153, 3224\u20133235 (2012).","journal-title":"Endocrinology"},{"key":"16796_CR8","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1210\/en.2015-1741","volume":"157","author":"C Willems","year":"2016","unstructured":"Willems, C. et al. Regeneration in the pituitary after cell-ablation injury: time-related aspects and molecular analysis. Endocrinology \n                           157, 705\u2013721 (2016).","journal-title":"Endocrinology"},{"key":"16796_CR9","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2013.07.004","volume":"13","author":"CL Andoniadou","year":"2013","unstructured":"Andoniadou, C. L. et al. Sox2(+) stem\/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell \n                           13, 433\u2013445 (2013).","journal-title":"Cell Stem Cell"},{"key":"16796_CR10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.stem.2013.07.006","volume":"13","author":"K Rizzoti","year":"2013","unstructured":"Rizzoti, K., Akiyama, H. & Lovell-Badge, R. Mobilized adult pituitary stem cells contribute to endocrine regeneration in response to physiological demand. Cell Stem Cell \n                           13, 419\u2013432 (2013).","journal-title":"Cell Stem Cell"},{"key":"16796_CR11","doi-asserted-by":"publisher","first-page":"11482","DOI":"10.1073\/pnas.1101553108","volume":"108","author":"C Gaston-Massuet","year":"2011","unstructured":"Gaston-Massuet, C. et al. Increased Wingless (Wnt) signaling in pituitary progenitor\/stem cells gives rise to pituitary tumors in mice and humans. Proc. Natl. Acad. Sci. USA \n                           108, 11482\u201311487 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"16796_CR12","doi-asserted-by":"publisher","first-page":"e4815","DOI":"10.1371\/journal.pone.0004815","volume":"4","author":"M Garcia-Lavandeira","year":"2009","unstructured":"Garcia-Lavandeira, M. et al. A GRFa2\/Prop1\/stem (GPS) cell niche in the pituitary. PLoS One \n                           4, e4815 (2009).","journal-title":"PLoS One"},{"key":"16796_CR13","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s00441-013-1713-8","volume":"354","author":"M Chen","year":"2013","unstructured":"Chen, M. et al. Coxsackievirus and adenovirus receptor-positive cells compose the putative stem\/progenitor cell niches in the marginal cell layer and parenchyma of the rat anterior pituitary. Cell Tissue Res. \n                           354, 823\u2013836 (2013).","journal-title":"Cell Tissue Res."},{"key":"16796_CR14","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/BF00318674","volume":"261","author":"E Carbajo-P\u00e9rez","year":"1990","unstructured":"Carbajo-P\u00e9rez, E. & Watanabe, Y. G. Cellular proliferation in the anterior pituitary of the rat during the postnatal period. Cell Tissue Res. \n                           261, 333\u2013338 (1990).","journal-title":"Cell Tissue Res."},{"key":"16796_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00429-002-0271-8","volume":"206","author":"Y Taniguchi","year":"2002","unstructured":"Taniguchi, Y., Yasutaka, S., Kominami, R. & Shinohara, H. Proliferation and differentiation of rat anterior pituitary cells. Anat. Embryol. \n                           206, 1\u201311 (2002).","journal-title":"Anat. Embryol."},{"key":"16796_CR16","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1089\/scd.2011.0496","volume":"21","author":"L Gremeaux","year":"2012","unstructured":"Gremeaux, L., Fu, Q., Chen, J. & Vankelecom, H. Activated phenotype of the pituitary stem\/progenitor cell compartment during the early-postnatal maturation phase of the gland. Stem Cells Dev. \n                           21, 801\u2013813 (2012).","journal-title":"Stem Cells Dev."},{"key":"16796_CR17","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1111\/j.1365-2826.2006.01459.x","volume":"18","author":"L Nolan","year":"2006","unstructured":"Nolan, L. & Levy, A. A population of non-luteinising hormone\/non-adrenocorticotrophic hormone-positive cells in the male rat anterior pituitary responds mitotically to both gonadectomy and adrenalectomy. J Neuroendocr. \n                           18, 655\u2013661 (2006).","journal-title":"J Neuroendocr."},{"key":"16796_CR18","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1038\/ncb3434","volume":"18","author":"L Blaas","year":"2016","unstructured":"Blaas, L. et al. Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours. Nat. Cell Biol. \n                           18, 1346\u20131356 (2016).","journal-title":"Nat. Cell Biol."},{"key":"16796_CR19","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/ncb3535","volume":"19","author":"JD Hoeck","year":"2017","unstructured":"Hoeck, J. D. et al. Stem cell plasticity enables hair regeneration following Lgr5+ cell loss. Nat. Cell Biol. \n                           19, 666\u2013676 (2017).","journal-title":"Nat. Cell Biol."},{"key":"16796_CR20","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/nature23282","volume":"548","author":"Y Zhang","year":"2017","unstructured":"Zhang, Y. et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature \n                           548, 52\u201357 (2017).","journal-title":"Nature"},{"key":"16796_CR21","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature10408","volume":"478","author":"H Tian","year":"2011","unstructured":"Tian, H. et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature \n                           478, 255\u2013259 (2011).","journal-title":"Nature"},{"key":"16796_CR22","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1073\/pnas.1118857109","volume":"109","author":"K Yan","year":"2012","unstructured":"Yan, K., Chia, L. & Li, X. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Pnas \n                           109, 466\u2013471 (2012).","journal-title":"Pnas"},{"key":"16796_CR23","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1242\/dev.131490","volume":"143","author":"VF Vallone","year":"2016","unstructured":"Vallone, V. F. et al. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage. Development \n                           143, 1452\u20131463 (2016).","journal-title":"Development"},{"key":"16796_CR24","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/nm1328","volume":"11","author":"M Ito","year":"2005","unstructured":"Ito, M. et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat. Med. \n                           11, 1351\u20131354 (2005).","journal-title":"Nat. Med."},{"key":"16796_CR25","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nature11826","volume":"494","author":"M Huch","year":"2013","unstructured":"Huch, M. et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature \n                           494, 247\u2013250 (2013).","journal-title":"Nature"},{"key":"16796_CR26","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1210\/en.2005-0185","volume":"146","author":"J Chen","year":"2005","unstructured":"Chen, J. et al. The adult pituitary contains a cell population displaying stem\/progenitor cell and early embryonic characteristics. Endocrinology \n                           146, 3985\u20133998 (2005).","journal-title":"Endocrinology"},{"key":"16796_CR27","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1530\/ERC-14-0546","volume":"22","author":"F Mertens","year":"2015","unstructured":"Mertens, F. et al. Pituitary tumors contain a side population with tumor stem cell-associated characteristics. Endocr. Relat. Cancer \n                           22, 481\u2013504 (2015).","journal-title":"Endocr. Relat. Cancer"},{"key":"16796_CR28","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1242\/dev.148478","volume":"144","author":"M Boretto","year":"2017","unstructured":"Boretto, M. et al. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development \n                           144, 1775\u20131786 (2017).","journal-title":"Development"},{"key":"16796_CR29","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1093\/bioinformatics\/bth254","volume":"20","author":"OJ Marshall","year":"2004","unstructured":"Marshall, O. J. PerlPrimer: Cross-platform, graphical primer design for standard, bisulphite and real-time PCR. Bioinformatics \n                           20, 2471\u20132472 (2004).","journal-title":"Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16796-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16796-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16796-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T15:08:37Z","timestamp":1671808117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16796-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,5]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["16796"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-16796-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,5]]},"assertion":[{"value":"14 July 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16940"}}