Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation

Robin D. Lee, Sarah A. Munro, Todd P. Knutson, Rebecca S. LaRue, Lynn M. Heltemes-Harris and Michael A. Farrar ()
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Robin D. Lee: University of Minnesota
Sarah A. Munro: University of Minnesota
Todd P. Knutson: University of Minnesota
Rebecca S. LaRue: University of Minnesota
Lynn M. Heltemes-Harris: University of Minnesota
Michael A. Farrar: University of Minnesota

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Integration of external signals and B-lymphoid transcription factor activities organise B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We use single-cell transcriptomics/proteomics to identify differentially expressed gene networks across B cell development and correlate these networks with subtypes of B cell leukemia. Here we show unique transcriptional signatures that refine the pre-B cell expansion stages into pre-BCR-dependent and pre-BCR-independent proliferative phases. These changes correlate with reciprocal changes in expression of the transcription factor EBF1 and the RNA binding protein YBX3, that are defining features of the pre-BCR-dependent stage. Using pseudotime analysis, we further characterize the expression kinetics of different biological modalities across B cell development, including transcription factors, cytokines, chemokines, and their associated receptors. Our findings demonstrate the underlying heterogeneity of developing B cells and characterise developmental nodes linked to B cell transformation.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27232-5

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DOI: 10.1038/s41467-021-27232-5

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