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Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis.

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, 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.



PROVIDER: S-EPMC6028518 | BioStudies | 2018-01-01

SECONDARY ACCESSION(S): 10.15252/embj.201797105

REPOSITORIES: biostudies

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Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors.

Alberti-Servera Llucia L   von Muenchow Lilly L   Tsapogas Panagiotis P   Capoferri Giuseppina G   Eschbach Katja K   Beisel Christian C   Ceredig Rhodri R   Ivanek Robert R   Rolink Antonius A  

The EMBO journal 20171013 24

Single-cell RNA sequencing is a powerful technology for assessing heterogeneity within defined cell populations. Here, we describe the heterogeneity of a B220+CD117intCD19-NK1.1- uncommitted hematopoietic progenitor having combined lymphoid and myeloid potential. Phenotypic and functional assays revealed four subpopulations within the progenitor with distinct lineage developmental potentials. Among them, the Ly6D+SiglecH-CD11c- fraction was lymphoid-restricted exhibiting strong B-cell potential,  ...[more]

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