Junctional Adhesion Molecule 2 Represents a Subset of Hematopoietic Stem Cells with Enhanced Potential for T Lymphopoiesis

Research output: Contribution to journalArticle

Abstract

The distinct lineage potential is a key feature of hematopoietic stem cell (HSC) heterogeneity, but a subset of HSCs specialized for a single lymphoid compartment has not been identified. Here we report that HSCs expressing junctional adhesion molecule 2 (Jam2) at a higher level (Jam2high HSCs) have a greater T cell reconstitution capacity. Jam2high HSCs are metabolically dormant but preferentially differentiate toward lymphocytes, especially T cell lineages. Jam2high HSCs uniquely express T cell-related genes, and the interaction with Jam1 facilitates the Notch/Delta signaling pathway. Frequency of Jam2high HSCs changes upon T cell depletion in vivo, potentially suggesting that Jam2 expression may reflect scarcity of T cells and requirement of T cell replenishment. Our findings highlight Jam2 as a potential marker for a subfraction of HSCs with an extensive lymphopoietic capacity, mainly in T lymphopoiesis. Radulovic et al. show that hematopoietic stem cells expressing Jam2 at a higher level on their cell surface (Jam2high HSCs) have a greater lymphopoietic potential, particularly T cells. Interaction with Jam1 facilitates Notch/Delta signals, which might be the potential mechanism. The frequency of Jam2high HSCs changes upon selective hematopoietic stress.

Details

Authors
Organisations
External organisations
  • Kyoto University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • hematopoietic stem cell, Jam2, junctional adhesion molecule, Notch signal, stem cell heterogeneity, T cell
Original languageEnglish
Pages (from-to)2826-2836.e5
JournalCell Reports
Volume27
Issue number10
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes