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

Nat Commun. 2021 Nov 25;12(1):6843. doi: 10.1038/s41467-021-27232-5.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Proliferation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Leukopoiesis / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / metabolism
  • Prognosis
  • Proteomics
  • Single-Cell Analysis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • CCAAT-Enhancer-Binding Proteins
  • EBF1 protein, human
  • Heat-Shock Proteins
  • Trans-Activators
  • YBX3 protein, human