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However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative stress has never been investigated genetically. We assessed the functional sources of THPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a\n                    <jats:italic>Thpo<\/jats:italic>\n                    translational reporter, we found that the liver but not the bone marrow is the major source of THPO protein after myeloablation. Mice with conditional\n                    <jats:italic>Thpo<\/jats:italic>\n                    deletion from osteoblasts and\/or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional\n                    <jats:italic>Thpo<\/jats:italic>\n                    deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic THPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.\n                  <\/jats:p>","DOI":"10.7554\/elife.69894","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:01:01Z","timestamp":1630396861000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69894","source":"Crossref","is-referenced-by-count":8,"title":["Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-8471","authenticated-orcid":true,"given":"Longfei","family":"Gao","sequence":"first","affiliation":[{"name":"Columbia Stem Cell Initiative, Columbia University Medical Center","place":["New York, United States"]},{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University Medical Center","place":["New York, United States"]},{"name":"Department of 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