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We used an unbiased<jats:italic>in vivo<\/jats:italic>chemical screen in a transgenic (<jats:italic>c-myb:EGFP<\/jats:italic>) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both<jats:italic>in vivo<\/jats:italic>and during<jats:italic>ex vivo<\/jats:italic>expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice. Interestingly, VPA increased CD34<jats:sup>+<\/jats:sup>cell adhesion to primary mesenchymal stromal cells and reduced their<jats:italic>in vitro<\/jats:italic>chemokine-mediated migration capacity. In line with this, VPA-treated human CD34<jats:sup>+<\/jats:sup>cells showed reduced homing and early engraftment in a xenograft transplant model, but retained their long-term engraftment potential<jats:italic>in vivo<\/jats:italic>, and maintained their differentiation ability both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. In summary, our data demonstrate that certain HDACIs lead to a net expansion of hHSPCs with retained long-term engraftment potential and could be further explored as candidate compounds to amplify<jats:italic>ex-vivo<\/jats:italic>engineered peripheral blood stem cells.<\/jats:p>","DOI":"10.1038\/s41598-017-12360-0","type":"journal-article","created":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T11:09:50Z","timestamp":1505473790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Guruchandar","family":"Arulmozhivarman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7122-7331","authenticated-orcid":false,"given":"Martin","family":"Kr\u00e4ter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manja","family":"Wobus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Friedrichs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham Pishali","family":"Bejestani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Alexopoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-8371","authenticated-orcid":false,"given":"Andreas","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"St\u00f6ter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-1869","authenticated-orcid":false,"given":"Marc","family":"Bickle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nona","family":"Shayegi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2421-6127","authenticated-orcid":false,"given":"Jochen","family":"Hampe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"St\u00f6lzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Brand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-0031","authenticated-orcid":false,"given":"Malte","family":"von Bonin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bornh\u00e4user","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,9,21]]},"reference":[{"key":"12360_CR1","doi-asserted-by":"publisher","unstructured":"Niederwieser, D. et al. 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