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| Status |
Public on Nov 29, 2014 |
| Title |
The NFKB inducing kinase (NIK) modulates hematopoiesis during stress |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The genetic programs that maintain hematopoiesis during steady state in physiologic conditions are different from those activated during stress. Here we show that hematopoietic stem cells (HSCs) with deficiencies in components of the alternative NFkB pathway (the NFkB inducing kinase, NIK, and the downstream molecule NFkB2) 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, i.e., either NFkB2 or c-Rel, only NFkB2 deficiency recapitulated the defects detected with NIK-deficient HSCs. Our results underscore the role of NIK and the alternative NFkB pathway for the recovery of normal levels of hematopoiesis after stress.
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| Overall design |
To explore the consequences of the defective NIKaly/aly protein in alternative NFKB signalling in HSCs, we investigated the gene expression profile of highly purified fresh LSK cells isolated from NIKWT and NIKaly/aly mice. We performed microarray analysis using total RNA from sorted LSK population using Agilent Whole Mouse Genome Oligo Microarrays.
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| Contributor(s) |
Gonzalez-Murillo A |
| Citation missing |
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| Submission date |
Nov 28, 2014 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Gustavo J Melen |
| E-mail(s) |
gustavo.melen@salud.madrid.org
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| Organization name |
FIB Hospital NIño Jesus
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| Street address |
Avda. Menendez Pelayo 65
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| City |
MAdrid |
| State/province |
Madrid |
| ZIP/Postal code |
28009 |
| Country |
Spain |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA268831 |
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