{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:41:29Z","timestamp":1791157289221,"version":"4.1.0"},"reference-count":42,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study investigated the potential role of stromal cell\u2013derived factor 1 (SDF-1) in human intrathymic T-cell differentiation. Results show that SDF-1 is produced by human thymic epithelial cells from the subcapsular and medullary areas, and its receptor, CXCR4, is up-regulated on CD34+ precursor cells committed to the T-cell lineage. Chimeric human-mouse fetal thymus organ culture (FTOC) seeded with purified CD34+thymic progenitors and treated with neutralizing antibodies against SDF-1 or CXCR4 showed a significant reduction of the number of human thymocytes and an arrested thymocyte differentiation in the transition between CD34+ precursor cells and CD4+ immature thymocytes. SDF-1\u2013treated FTOC showed an increase of human thymocyte numbers, mainly affecting the most immature subpopulations. Moreover, these results suggest that CXCR4\/SDF-1 signaling is not critical for the CD34+ cell precursor recruitment to the thymus. On the other hand, SDF-1 significantly increased the viability of CD34+ T-cell precursors modulating the expression ofBCL-2 and BAX genes, and stimulated the proliferation of CD34+ thymic precursor cells, particularly in synergy with interleukin 7 (IL-7), but not with other cytokines, such as stem cell factor or flt3-ligand. Accordingly, only IL-7 was able to up-regulate CXCR4 expression on CD34+ thymic progenitors. In addition, deprivation of SDF-1 partially inhibited human thymocyte expansion induced by IL-7 in human-mouse FTOC. This study indicates that SDF-1\/CXCR4 signaling is required for the survival, expansion, and subsequent differentiation of human early thymocytes and identifies a new mechanism by which IL-7 mediates its effects on human thymopoiesis.<\/jats:p>","DOI":"10.1182\/blood.v99.2.546","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"546-554","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":103,"title":["Stromal cell\u2013derived factor 1\/CXCR4 signaling is critical for early human T-cell development"],"prefix":"10.1182","volume":"99","author":[{"given":"Carmen","family":"Herna\u0301ndez-Lo\u0301pez","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology, Faculty of Biology, and Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Varas","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Faculty of Biology, and Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Sacedo\u0301n","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Faculty of Biology, and Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Jime\u0301nez","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Faculty of Biology, and Department of Cell Biology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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