Transcriptomics

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Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a [wildtype tissue]


ABSTRACT: Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells. 4 individual sorts of Fr.A and Fr.B/C fractions in bone marrow and fetal liver of BALB/c mice

ORGANISM(S): Mus musculus  

SUBMITTER: Yue-Sheng Li  Kyoko Hayakawa   Susan A Shinton   Richard R Hardy   Lingjuan Tang   Richard R. Hardy   Yan Zhou   Srinivasa Bandi    

PROVIDER: E-GEOD-65533 | ArrayExpress | 2015-03-01

SECONDARY ACCESSION(S): GSE65533PRJNA274289

REPOSITORIES: GEO, ArrayExpress

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