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Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
Lund Univ, Sweden.
Lund Univ, Sweden.
Lund Univ, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
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2018 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 215, no 7, p. 1947-1963Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ROCKEFELLER UNIV PRESS , 2018. Vol. 215, no 7, p. 1947-1963
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-150275DOI: 10.1084/jem.20171384ISI: 000440822900015PubMedID: 29899037OAI: oai:DiVA.org:liu-150275DiVA, id: diva2:1239708
Note

Funding Agencies|Swedish Cancer Society; Swedish Childhood Cancer Foundation; Swedish Research Council; Knut and Alice Wallenbergs Foundation

Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-09-07

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