Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

Christina T Jensen, Josefine Åhsberg, Mikael N E Sommarin, Tobias Strid, Rajesh Somasundaram, Kazuki Okuyama, Jonas Ungerbäck, Jussi Kupari, Matti S Airaksinen, Stefan Lang, David Bryder, Shamit Soneji, Göran Karlsson, Mikael Sigvardsson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)1947-1963
Antal sidor17
TidskriftJournal of Experimental Medicine
Volym215
Nummer7
DOI
StatusPublished - 2018 juli 2

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi
  • Immunologi inom det medicinska området

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