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

doi:10.1016/j.celrep.2019.05.028

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

Cell Rep. 2019 Jun 4;27(10):2826-2836.e5. doi: 10.1016/j.celrep.2019.05.028.

Authors

Visnja Radulovic¹, Mark van der Garde¹, Shuhei Koide¹, Valgardur Sigurdsson¹, Stefan Lang², Shin Kaneko³, Kenichi Miharada⁴

Affiliations

¹ Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
² StemTherapy Bioinformatics Core Facility, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
³ Center of iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan.
⁴ Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: kenichi.miharada@med.lu.se.

PMID: 31167130
DOI: 10.1016/j.celrep.2019.05.028

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 (Jam2^high HSCs) have a greater T cell reconstitution capacity. Jam2^high HSCs are metabolically dormant but preferentially differentiate toward lymphocytes, especially T cell lineages. Jam2^high HSCs uniquely express T cell-related genes, and the interaction with Jam1 facilitates the Notch/Delta signaling pathway. Frequency of Jam2^high 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.

Keywords: Jam2; Notch signal; T cell; hematopoietic stem cell; junctional adhesion molecule; stem cell heterogeneity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Animals
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / metabolism
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism
Cell Lineage
Female
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Junctional Adhesion Molecule B / genetics
Junctional Adhesion Molecule B / metabolism*
Lymphopoiesis / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Receptor, Notch3 / genetics
Receptor, Notch3 / metabolism
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Recombinant Proteins
T-Lymphocytes / cytology*
T-Lymphocytes / metabolism

Substances

Adaptor Proteins, Signal Transducing
Calcium-Binding Proteins
Cell Adhesion Molecules
DLL4 protein, mouse
F11R protein, human
Junctional Adhesion Molecule B
Notch3 protein, mouse
Receptor, Notch3
Receptors, Cell Surface
Recombinant Proteins