Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

Research output: Contribution to journalArticle

Abstract

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19+ progenitor compartment.

Details

Authors
Organisations
External organisations
  • Linköping University
  • University of Helsinki
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Immunology in the medical area
Original languageEnglish
Pages (from-to)1947-1963
JournalJournal of Experimental Medicine
Volume215
Issue number7
Publication statusPublished - 2018 Jul 2
Publication categoryResearch
Peer-reviewedYes