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Here, we show that hematopoietic stem cells (HSCs) with deficiencies in components of the alternative NF\u03baB pathway (the NF\u03baB inducing kinase, NIK, and the downstream molecule NF\u03baB2) had a defect in response to stressors such as supraphysiological doses of cytokines, chemotherapy, and hematopoietic transplantation. NIK-deficient mice had peripheral blood and bone marrow leukocyte numbers within normal ranges (except for the already reported defects in B-cell maturation); however, HSCs showed significantly slower expansion capacity in in vitro cultures compared to wild-type HSCs. This was due to a delayed cell cycle and increased apoptosis. In vivo experiments showed that NIK-deficient HSCs did not recover at the same pace as controls when challenged with myeloablative chemotherapy. Finally, NIK-deficient HSCs showed a significantly decreased competitive repopulation capacity in vivo. Using HSCs from mice deficient in one of two downstream targets of NIK, that is, either NF\u03baB2 or c-Rel, only NF\u03baB2 deficiency recapitulated the defects detected with NIK-deficient HSCs. Our results underscore the role of NIK and the alternative NF\u03baB pathway for the recovery of normal levels of hematopoiesis after stress. Stem Cells \u00a02015;33:2825\u20132837<\/jats:p>","DOI":"10.1002\/stem.2066","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T21:01:04Z","timestamp":1433278864000},"page":"2825-2837","source":"Crossref","is-referenced-by-count":30,"title":["The NFKB Inducing Kinase Modulates Hematopoiesis During Stress"],"prefix":"10.1093","volume":"33","author":[{"given":"\u00c1frica","family":"Gonz\u00e1lez-Murillo","sequence":"first","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital Universitario Ni\u00f1o Jes\u00fas, and Instituto de Investigaci\u00f3n Sanitaria La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital Universitario Ni\u00f1o Jes\u00fas, and Instituto de Investigaci\u00f3n Sanitaria La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Baena","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital Universitario Ni\u00f1o Jes\u00fas, and Instituto de Investigaci\u00f3n Sanitaria La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo J.","family":"Melen","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital Universitario Ni\u00f1o Jes\u00fas, and Instituto de Investigaci\u00f3n Sanitaria La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Cell Differentiation and Cytometry Unit, Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER-ER), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"S\u00e1nchez-Valdepe\u00f1as","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology department Centro de Biolog\u00eda Molecular Severo Ochoa, Cantoblanco, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 C.","family":"Segovia","sequence":"additional","affiliation":[{"name":"Cell Differentiation and Cytometry Unit, Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER-ER), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiou-Chi","family":"Liou","sequence":"additional","affiliation":[{"name":"Immunology, Cornell University Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Schmid","sequence":"additional","affiliation":[{"name":"II, Medizinische Klinik, Technische Universit\u00e4t, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds","family":"Madero","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital Universitario Ni\u00f1o Jes\u00fas, and Instituto de Investigaci\u00f3n Sanitaria La Princesa, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Fresno","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology department Centro de Biolog\u00eda Molecular Severo Ochoa, Cantoblanco, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Oncohematolog\u00eda, FIB Hospital 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