Advanced

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 , 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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
215
issue
7
pages
1947 - 1963
publisher
Rockefeller University Press
external identifiers
  • scopus:85049460005
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
2019-04-10 04:12:14
@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},
  volume       = {215},
  year         = {2018},
}