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Although some histone deacetylase (HDAC) inhibitors, such as valproic acid (VA), induce differentiation and apoptosis in a variety of leukemic cells in vitro, they produce a favorable effect on the expansion of normal HSCs. In this study, we have identified the VA target HDAC3 as a negative regulator of umbilical cord blood HSC expansion. We demonstrate that knockdown of the transcript dramatically improves CD34+ cell expansion, which correlates with a higher potential to generate colony-forming units in functional assays. We show that this effect is mediated at the level of primitive hematopoietic cells and that it is not due to negative effects on specific cell commitment or alterations in the cell cycle. HDAC3 inhibition does not block commitment to the monocytic lineage and the maturation of monocyte precursors, which are the main inhibited pathways in the presence of VA. Therefore, our results identify HDAC3 as a promising target for therapies aiming to expand HSCs.<\/jats:p>","DOI":"10.1089\/scd.2011.0698","type":"journal-article","created":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T15:44:56Z","timestamp":1332949496000},"page":"2581-2591","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Histone Deacetylase 3 Modulates the Expansion of Human Hematopoietic Stem Cells"],"prefix":"10.1177","volume":"21","author":[{"given":"Carina","family":"Elizalde","sequence":"first","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Fern\u00e1ndez-Rueda","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Salcedo","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akaitz","family":"Dorronsoro","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izaskun","family":"Ferrin","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Jakobsson","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Trigueros","sequence":"additional","affiliation":[{"name":"Mesenchymal and Hematopoietic Stem Cell Lab, Fundaci\u00f3n Inbiomed, Paseo Mikeletegi, San Sebasti\u00e1n, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,3,28]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9836"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.284"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0544"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0516"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.10.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0256"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3011"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3063"},{"key":"e_1_3_3_10_2","first-page":"347","article-title":"Actions of sodium valproate on the central nervous system","volume":"50","author":"Tunnicliff G","year":"1999","unstructured":"Tunnicliff G. 1999. 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