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However, the mechanism underlying its biological effect is unknown, and its differences from other TPO receptor agonists remain unclear. Therefore, we determined the in vitro expansion effect of romiplostim on human CD34\u2009+\u2009hematopoietic stem and progenitor cells (HSPCs) versus recombinant human TPO (rhTPO) and another clinically available drug, eltrombopag. We also performed single-cell RNA-seq to determine effects of romiplostim on CD34\u2009+\u2009HSPCs at the molecular level. The maximum expansion effect of romiplostim on total CD34\u2009+\u2009cells, CD34\u2009+\u2009CD38\u2009+\u2009progenitor cells, and CD34\u2009+\u2009CD38\u2009\u2212\u2009immature cells was comparable to that of rhTPO, but higher than that of eltrombopag, particularly on CD34\u2009+\u2009CD38\u2009\u2212\u2009immature cells. Single-cell RNA-seq analysis revealed that both romiplostim and eltrombopag induced signatures driven by rhTPO, but romiplostim induced molecular changes related to RHOA signaling in the most primitive HSPC subsets that were partially driven or not driven by eltrombopag. Additionally, romiplostim did not induce <jats:italic>TFRC<\/jats:italic> expression as was observed with eltrombopag. In conclusion, romiplostim expands and affects human HSPCs similar to rhTPO, but partially different from eltrombopag in terms of induction of gene expression.<\/jats:p>","DOI":"10.1007\/s12185-024-03853-6","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T11:01:54Z","timestamp":1726830114000},"page":"575-586","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus thrombopoietin and eltrombopag"],"prefix":"10.1007","volume":"120","author":[{"given":"Yuta","family":"Tezuka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Onoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Morishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Sumitomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Nishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Takizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"issue":"3","key":"3853_CR1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1182\/blood-2016-01-636381","volume":"128","author":"S Ogawa","year":"2016","unstructured":"Ogawa S. 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