{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:46:14Z","timestamp":1791326774106,"version":"4.3.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,7,18]]},"abstract":"<jats:p>\n                    The spermatogonial stem cell initiates and maintains spermatogenesis in the testis. To perform this role, the stem cell must self replicate as well as produce daughter cells that can expand and differentiate to form spermatozoa. Despite the central importance of the spermatogonial stem cell to male reproduction, little is known about its morphological or biochemical characteristics. This results, in part, from the fact that spermatogonial stem cells are an extremely rare cell population in the testis, and techniques for their enrichment are just beginning to be established. In this investigation, we used a multiparameter selection strategy, combining the\n                    <jats:italic>in vivo<\/jats:italic>\n                    cryptorchid testis model with\n                    <jats:italic>in vitro<\/jats:italic>\n                    fluorescence-activated cell sorting analysis. Cryptorchid testis cells were fractionated by fluorescence-activated cell sorting analysis based on light-scattering properties and expression of the cell surface molecules \u03b16-integrin, \u03b1v-integrin, and the c-kit receptor. Two important observations emerged from these analyses. First, spermatogonial stem cells from the adult cryptorchid testis express little or no c-kit. Second, the most effective enrichment strategy, in this study, selected cells with low side scatter light-scattering properties, positive staining for \u03b16-integrin, and negative or low \u03b1v-integrin expression, and resulted in a 166-fold enrichment of spermatogonial stem cells. Identification of these characteristics will allow further purification of these valuable cells and facilitate the investigation of molecular mechanisms governing spermatogonial stem cell self renewal and hierarchical differentiation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.15.8346","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"8346-8351","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":329,"title":["Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells"],"prefix":"10.1073","volume":"97","author":[{"given":"Takashi","family":"Shinohara","sequence":"first","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle E.","family":"Orwig","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary R.","family":"Avarbock","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph L.","family":"Brinster","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,7,18]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"43","volume-title":"Oxford Textbook of Pathology","author":"Potten C S","year":"1992","unstructured":"C S Potten Oxford Textbook of Pathology, eds J O McGee, P G Isaacson, N A Wright (Oxford Univ. Press, Oxford), pp. 43\u201352 (1992)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/oso\/9780195062694.003.0012","volume-title":"Cell and Molecular Biology of the Testis","author":"Meistrich M L","year":"1993","unstructured":"M L Meistrich, M E A B van Beek Cell and Molecular Biology of the Testis, eds C Desjardins, L L Ewing (Oxford Univ. Press, New York), pp. 266\u2013295 (1993)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(93)90159-D"},{"key":"e_1_3_3_4_2","first-page":"251","volume":"15","author":"Micklem H S","year":"1987","unstructured":"H S Micklem, J E Lennon, J D Ansell, R A Gray Exp Hematol 15, 251\u2013257 (1987).","journal-title":"Exp Hematol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.3.822"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110611"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2307\/3570892"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V55.1.77.77"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(89)90192-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2788"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5272.242"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11303"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11298"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod60.6.1429"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5504"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9655"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1998.tb01318.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)43045-1"},{"key":"e_1_3_3_19_2","first-page":"111","volume":"41","author":"Ogawa T","year":"1997","unstructured":"T Ogawa, J M Ar\u00e9chaga, M R Avarbock, R L Brinster Int J Dev Biol 41, 111\u2013122 (1997).","journal-title":"Int J Dev Biol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2795(199906)53:2<142::AID-MRD3>3.0.CO;2-O"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830091105"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.8.1655"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod34.4.613"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod53.5.1003"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990190404"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod59.1.84"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.2.689"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.22.4585"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod61.3.582"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.12.7172"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80018-7"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091180202"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.11.5565"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1402420116"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0320"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(93)25006-N"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod55.4.822"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/j.1939-4640.1995.tb00550.x","volume":"16","author":"Orth J M","year":"1995","unstructured":"J M Orth, W F Jester J Androl 16, 389\u2013399 (1995).","journal-title":"J Androl"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00287-7"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0378(87)90069-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.97.15.8346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:04:04Z","timestamp":1704326644000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.97.15.8346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7,18]]},"references-count":40,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2000,7,18]]}},"alternative-id":["10.1073\/pnas.97.15.8346"],"URL":"https:\/\/doi.org\/10.1073\/pnas.97.15.8346","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,7,18]]},"assertion":[{"value":"2000-06-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-07-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}