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Anemia and hematopoietic disorders are observed in astronauts after spaceflight. Hematopoietic stem and progenitor cells (HSPCs), which can self\u2010renew and give rise to all blood cells, play vital roles in hematopoiesis and homeostasis; however, the molecular mechanisms responsible for the impacts of microgravity on the proliferation of HSPCs remain unclear. We maintained mouse bone marrow HSPCs in the presence of stem cell factor for 12 d under spaceflight and simulated microgravity conditions, respectively, and analyzed cell proliferation and gene expression. Both spaceflight and simulated microgravity significantly decreased the number of HSPCs, mainly by blocking cell cycle at G\n                    <jats:sub>1<\/jats:sub>\n                    \/S transition, but did not affect their differentiation abilities. RNA\u2010sequencing data indicated that genes related to cell proliferation were down\u2010regulated, whereas the genes related to cell death were up\u2010regulated under microgravity. Among the gene signatures, we identified that the Kit\u2010Ras\/cAMP\u2013cAMP response element\u2010binding protein pathway might be one of the major microgravity\u2010regulated pathways during HSPC proliferation. Furthermore, the quantification of notable genes was validated at the mRNA levels under simulated microgravity condition. Overall, these results would help us to understand the intracellular molecular mechanisms regulating microgravity\u2010inhibited proliferation of HSPCs.\u2014Wang, P., Tian, H., Zhang, J., Qian, J., Li, L., Shi, L., Zhao, Y. Spaceflight\/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit\u2010Ras\/cAMP\u2010CREB pathway networks as evidenced by RNA\u2010Seq assays. FASEB J. 33, 5903\u20135913 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802413r","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T18:35:54Z","timestamp":1549391754000},"page":"5903-5913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Spaceflight\/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit\u2010Ras\/cAMP\u2010CREB pathway networks as evidenced by RNA\u2010Seq assays"],"prefix":"10.1096","volume":"33","author":[{"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Qian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology  Beijing China"},{"name":"Institute for Stem Cell and Regeneration Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0273-1177(02)00394-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00315"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.06.021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppl.12591"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29901"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0309167"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2005.05.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V60.5.1059.1059"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(02)00913-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004267193"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950181215"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0408"},{"key":"e_1_2_8_14_1","first-page":"730","article-title":"Effects of microgravity and increased gravity on bone marrow of rats","volume":"65","author":"Lange R. 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