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

Radulovic, Visnja LU ; van der Garde, Mark LU ; Koide, Shuhei LU ; Sigurdsson, Valgardur LU ; Lang, Stefan LU orcid ; Kaneko, Shin and Miharada, Kenichi LU (2019) In Cell Reports 27(10). p.5-2836
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hematopoietic stem cell, Jam2, junctional adhesion molecule, Notch signal, stem cell heterogeneity, T cell
in
Cell Reports
volume
27
issue
10
pages
5 - 2836
publisher
Cell Press
external identifiers
  • pmid:31167130
  • scopus:85065758169
ISSN
2211-1247
DOI
10.1016/j.celrep.2019.05.028
language
English
LU publication?
yes
id
605707a8-8ca7-4e4b-b49c-5b05ac072f09
date added to LUP
2019-06-17 11:31:00
date last changed
2025-10-14 10:46:51
@article{605707a8-8ca7-4e4b-b49c-5b05ac072f09,
  abstract     = {{<p>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 (Jam2<sup>high</sup> HSCs) have a greater T cell reconstitution capacity. Jam2<sup>high</sup> HSCs are metabolically dormant but preferentially differentiate toward lymphocytes, especially T cell lineages. Jam2<sup>high</sup> HSCs uniquely express T cell-related genes, and the interaction with Jam1 facilitates the Notch/Delta signaling pathway. Frequency of Jam2<sup>high</sup> 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 (Jam2<sup>high</sup> 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 Jam2<sup>high</sup> HSCs changes upon selective hematopoietic stress.</p>}},
  author       = {{Radulovic, Visnja and van der Garde, Mark and Koide, Shuhei and Sigurdsson, Valgardur and Lang, Stefan and Kaneko, Shin and Miharada, Kenichi}},
  issn         = {{2211-1247}},
  keywords     = {{hematopoietic stem cell; Jam2; junctional adhesion molecule; Notch signal; stem cell heterogeneity; T cell}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{5--2836}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Junctional Adhesion Molecule 2 Represents a Subset of Hematopoietic Stem Cells with Enhanced Potential for T Lymphopoiesis}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2019.05.028}},
  doi          = {{10.1016/j.celrep.2019.05.028}},
  volume       = {{27}},
  year         = {{2019}},
}