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

Visnja Radulovic, Mark van der Garde, Shuhei Koide, Valgardur Sigurdsson, Stefan Lang, Shin Kaneko, Kenichi Miharada

Research output: Contribution to journalArticlepeer-review

6 Citations (SciVal)

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.

Original languageEnglish
Pages (from-to)2826-2836.e5
JournalCell Reports
Volume27
Issue number10
DOIs
Publication statusPublished - 2019

Subject classification (UKÄ)

  • Cell and Molecular Biology

Keywords

  • hematopoietic stem cell
  • Jam2
  • junctional adhesion molecule
  • Notch signal
  • stem cell heterogeneity
  • T cell

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