Comparing RNA expression profiles of KALori and KANSL mouse lungs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE101759 | GEO | 2017/07/22
SECONDARY ACCESSION(S): PRJNA395371
REPOSITORIES: GEO
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Project description:IKKa, 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).
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