Unraveling the Sox4-orchestrated pro-B cell differentiation program: Intricate roles of the RAG and CK1ε genes (RNA array)

ABSTRACT: One of the main objective of this study is to identify Sox4 controlled gene networks and their roles in progenitor B cells. Commitment of hematopoietic stem cells to B lineage precursors and development of B lineage precursors into mature B cells is attained through the coordinated function of multiple signaling networks, which are in turn controlled through stringent functioning of stage-specific transcription factors. Here, we describe the essential role of Sox4, an HMG (high mobility group)-box-containing transactivator, in B cell development. In the absence of Sox4, differentiation from pre-pro B to pro-B, from pro-B fraction B to pro-B fraction C and further to the immature B cell stage was severely impaired. Loss of differentiation was associated with reduced expression of Rag1 and Rag2 and markedly reduced DJ (diverse, joining) and VDJ (variable DJ) recombination at immunoglobulin heavy chain gene loci. We uncovered Sox4-regulated transcriptional circuits and a landscape of Sox4-chromatin interactions in pro-B cells. Sox4 ensured the negative regulation of Wnt signaling, which is critical for self-renewal of hematopoietic stem cells and early progenitors, by inducing one of its downstream effectors, casein kinase 1 epsilon. Our findings suggest that Sox4 orchestrates a unique transcriptional program and coordinates multilevel control in the differentiation of early-stage B cells. Total RNA isolated from triplicate samples were used for each cell type. Gene expression signatures were compared between Sox4fl/fl and Sox4fl/fl SE-Cre progenitor B cells (Loss-of-function array); p190 Bcr-Abl-immortalized Sox4fl/fl SE-Cre HA and Sox4fl/fl SE-Cre HA-Sox4 progenitor B cells (Gain-of-function array).

ORGANISM(S): Mus musculus

SUBMITTER: Xiaoping Sun 

PROVIDER: E-GEOD-50065 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress