ArrayExpress Uploader0mousekinase dead knockin IKKαK44A/K44Awild typekinase dead knockin IKKαK44A/K44Akinase dead knockin IKKαK44A/K44Awild type6517arrayexpress_sid6IKKa, a major regulator of noncanonical and canonical NF-kB pathways, is essential for B-lymphocyte maturation and secondary lymph organ...E-GEOD-30363/profile/8773/arrayexpressuploader15bonebone marrowcellliverlymphlymphocyteorganDec.12, 2014Falseikk-alpha-inactivation-impairs-early-b-lymphopoiesE-GEOD-30363_A-AFFY-45IKK alpha inactivation impairs early B-lymphopoiesis during hematopoiesisNov.11, 2014IKKa, a major regulator of noncanonical and canonical NF-kB pathways, is essential for B-lymphocyte maturation and secondary lymph organ formation. No evidence of IKKa regulating early B cell development currently exists. Here we found reduced pre-pro-B and pro-B cells but increased myeloid-erythroid lineages in the bone marrow (BM) of knockin mice expressing reduced and kinase-dead IKKa (KA/KA). The KA/KA BM cells recaptured their defects in wild-type recipients and KA/KA fetal liver displayed reduced B cells but increased progenitors. IKKa inactivation impaired both NF-kB pathways and deregulated expression of many genes required for early B cell commitment and hematopoiesis, including downregulated Pax5, IRF4, and Ikaros expression, but increased C/EBPa, GATA1, and Stat3 levels. Reintroduced combined NF-kB components, Pax5, and IKKa promoted BM B cell differentiation and repressed myeloid-erythroid lineages. Our studies revealed a new function of IKKa in a coordinated development process of B-lineage and erythroid-myeloid lineages during hematopoiesis via multiple pathways. Microarray analysis was performed on RNA isolated from the BM of B220+ cells isolated from 4-week old WT and KA/KA mice using affymetrix mouse 430 2.0 array chip, containing 45,000 genes, at the Laboratory of Molecular Technology SAIC-Frederick. Data were normalized, and log2 transformations were generated using Partek software (St. Louis, MO, USA).http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-30363http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-30363/samples/