Cargando…

Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

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-a...

Descripción completa

Detalles Bibliográficos
Autores principales: Jensen, Christina T., Åhsberg, Josefine, Sommarin, Mikael N.E., Strid, Tobias, Somasundaram, Rajesh, Okuyama, Kazuki, Ungerbäck, Jonas, Kupari, Jussi, Airaksinen, Matti S., Lang, Stefan, Bryder, David, Soneji, Shamit, Karlsson, Göran, Sigvardsson, Mikael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028518/
https://www.ncbi.nlm.nih.gov/pubmed/29899037
http://dx.doi.org/10.1084/jem.20171384
_version_ 1783336780085329920
author Jensen, Christina T.
Åhsberg, Josefine
Sommarin, Mikael N.E.
Strid, Tobias
Somasundaram, Rajesh
Okuyama, Kazuki
Ungerbäck, Jonas
Kupari, Jussi
Airaksinen, Matti S.
Lang, Stefan
Bryder, David
Soneji, Shamit
Karlsson, Göran
Sigvardsson, Mikael
author_facet Jensen, Christina T.
Åhsberg, Josefine
Sommarin, Mikael N.E.
Strid, Tobias
Somasundaram, Rajesh
Okuyama, Kazuki
Ungerbäck, Jonas
Kupari, Jussi
Airaksinen, Matti S.
Lang, Stefan
Bryder, David
Soneji, Shamit
Karlsson, Göran
Sigvardsson, Mikael
author_sort Jensen, Christina T.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6028518
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-60285182019-01-02 Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis Jensen, Christina T. Åhsberg, Josefine Sommarin, Mikael N.E. Strid, Tobias Somasundaram, Rajesh Okuyama, Kazuki Ungerbäck, Jonas Kupari, Jussi Airaksinen, Matti S. Lang, Stefan Bryder, David Soneji, Shamit Karlsson, Göran Sigvardsson, Mikael J Exp Med Research Articles 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. Rockefeller University Press 2018-07-02 /pmc/articles/PMC6028518/ /pubmed/29899037 http://dx.doi.org/10.1084/jem.20171384 Text en © 2018 Jensen et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Jensen, Christina T.
Åhsberg, Josefine
Sommarin, Mikael N.E.
Strid, Tobias
Somasundaram, Rajesh
Okuyama, Kazuki
Ungerbäck, Jonas
Kupari, Jussi
Airaksinen, Matti S.
Lang, Stefan
Bryder, David
Soneji, Shamit
Karlsson, Göran
Sigvardsson, Mikael
Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title_full Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title_fullStr Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title_full_unstemmed Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title_short Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis
title_sort dissection of progenitor compartments resolves developmental trajectories in b-lymphopoiesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028518/
https://www.ncbi.nlm.nih.gov/pubmed/29899037
http://dx.doi.org/10.1084/jem.20171384
work_keys_str_mv AT jensenchristinat dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT ahsbergjosefine dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT sommarinmikaelne dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT stridtobias dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT somasundaramrajesh dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT okuyamakazuki dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT ungerbackjonas dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT kuparijussi dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT airaksinenmattis dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT langstefan dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT bryderdavid dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT sonejishamit dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT karlssongoran dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis
AT sigvardssonmikael dissectionofprogenitorcompartmentsresolvesdevelopmentaltrajectoriesinblymphopoiesis