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

Autor: Lee, Robin D., Munro, Sarah A., Knutson, Todd P., LaRue, Rebecca S., Heltemes-Harris, Lynn M., Farrar, Michael A.
Předmět:
Zdroj: Nature Communications; 11/25/2021, Vol. 12 Issue 1, p1-16, 16p
Abstrakt: 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. The characterisation of B cell progenitors could benefit from single cell RNA analysis. Here the authors show distinct transcriptional profiles of B cell progenitors which are dependent upon pre-BCR and these profiles can be related to B cell transformation in lymphoblastic leukaemia. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index