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Although previous studies examined several intrathymic mechanisms that negatively affect T lymphopoiesis, the extrathymic mechanisms remain poorly understood. Here, we report a dramatic decrease in the percentage of early T lineage progenitors (ETPs) in three models of sepsis in mice (cecal ligation and puncture, lipopolysaccharide continuous injection, and poly I:C continuous injection). However, septic mice did not show a decrease in the number of bone marrow (BM) precursor cells. Instead, the BM progenitors for ETPs expressed reduced mRNA levels of CC chemokine receptor (CCR) 7, CCR9 and P-selectin glycoprotein ligand 1, and exhibited impaired homing capacity in vitro and in vivo. Furthermore, RNA-Seq analysis and real-time PCR showed a marked downregulation of several lymphoid-related genes in hematopoietic stem and progenitor cells. Hematopoietic stem and progenitor cells differentiated into myeloid cells but failed to generate T lymphocytes in vitro and in vivo. Our results indicate that the depletion of ETPs in septic mice might be a consequence of an impaired migration of BM progenitors to the thymus, as well as a defect in lymphoid lineage commitment.<\/jats:p>","DOI":"10.1002\/stem.2464","type":"journal-article","created":{"date-parts":[[2016,7,16]],"date-time":"2016-07-16T07:56:44Z","timestamp":1468655804000},"page":"2902-2915","source":"Crossref","is-referenced-by-count":34,"title":["Sepsis-Induced Thymic Atrophy Is Associated with Defects in Early Lymphopoiesis"],"prefix":"10.1093","volume":"34","author":[{"given":"Yaxian","family":"Kong","sequence":"first","affiliation":[{"name":"Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Molecular Biomedicine (CMB), 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengya","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, 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