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Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

Jensen, Christina T LU ; Åhsberg, Josefine LU ; Sommarin, Mikael N E LU ; Strid, Tobias LU ; Somasundaram, Rajesh ; Okuyama, Kazuki ; Ungerbäck, Jonas LU ; Kupari, Jussi ; Airaksinen, Matti S and Lang, Stefan LU orcid , et al. (2018) In Journal of Experimental Medicine 215(7). p.1947-1963
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
215
issue
7
pages
17 pages
publisher
Rockefeller University Press
external identifiers
  • scopus:85049460005
  • pmid:29899037
ISSN
1540-9538
DOI
10.1084/jem.20171384
language
English
LU publication?
yes
id
7f61afe1-1a43-4086-a076-0c98cba9a9fc
date added to LUP
2018-08-24 14:57:44
date last changed
2024-04-01 09:20:17
@article{7f61afe1-1a43-4086-a076-0c98cba9a9fc,
  abstract     = {{<p>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.</p>}},
  author       = {{Jensen, Christina T and Åhsberg, Josefine and Sommarin, Mikael N E and Strid, Tobias and Somasundaram, Rajesh and Okuyama, Kazuki and Ungerbäck, Jonas and Kupari, Jussi and Airaksinen, Matti S and Lang, Stefan and Bryder, David and Soneji, Shamit and Karlsson, Göran and Sigvardsson, Mikael}},
  issn         = {{1540-9538}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1947--1963}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis}},
  url          = {{http://dx.doi.org/10.1084/jem.20171384}},
  doi          = {{10.1084/jem.20171384}},
  volume       = {{215}},
  year         = {{2018}},
}