Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity

Blood. 2010 Apr 1;115(13):2601-9. doi: 10.1182/blood-2009-08-236398. Epub 2009 Dec 8.

Abstract

To investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lambda5 reporter transgenic mice to Rag1-GFP knockin mice. This allowed us to subfractionate common lymphoid progenitors and pre-pro-B (fraction A) cells into lambda5(-)Rag1(low), lambda5(-)Rag1(high), and lambda5(+)Rag1(high) cells. Clonal in vitro differentiation analysis demonstrated that Rag1(low) cells gave rise to B/T and NK cells. Rag1(high) cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells, whereas the lambda5(+) cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1(high) populations. These cells also expressed a higher level of the surface protein LY6D, providing an additional tool for the analysis of early lymphoid development. These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / biosynthesis
  • Antigens, Ly / genetics
  • Biomarkers
  • Cell Lineage
  • Cells, Cultured / cytology
  • Cells, Cultured / metabolism
  • Coculture Techniques
  • Flow Cytometry
  • GPI-Linked Proteins
  • Gene Expression Profiling
  • Gene Knock-In Techniques
  • Genes, Reporter
  • Homeodomain Proteins / genetics
  • Killer Cells, Natural / cytology
  • Lymphocyte Subsets / cytology
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism
  • Lymphopoiesis
  • Mice
  • Mice, Transgenic
  • PAX5 Transcription Factor / biosynthesis
  • PAX5 Transcription Factor / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics

Substances

  • Antigens, Ly
  • Biomarkers
  • Ebf1 protein, mouse
  • GPI-Linked Proteins
  • Homeodomain Proteins
  • Ly6d protein, mouse
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Pou2af1 protein, mouse
  • Trans-Activators
  • RAG-1 protein