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 Tcell reconstitution capacity. Jam2high HSCs are metabolically dormant but preferentially differentiatetoward lymphocytes, especially Tcell lineages. Jam2high HSCs uniquely express Tcell-related genes, and the interaction with Jam1 facilitates the Notch/Delta signaling pathway. Frequency of Jam2high HSCs changes upon Tcell depletion invivo, potentially suggesting that Jam2 expression may reflect scarcity of Tcells and requirement of Tcell replenishment. Our findings highlight Jam2 as a potential marker for a subfraction of HSCs with an extensive lymphopoietic capacity, mainly in T lymphopoiesis.
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