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Cell stem cell· 2026Q1

EPCR expression marks CD150neg deeply dormant long-term hematopoietic stem cells

Dawn S. Lin, Isabell Alexandra Guckes, Ian Ghezzi, Pia Sommerkamp et al.

Short summary

A novel subset of long-term hematopoietic stem cells (LT-HSCs), termed LT-HSC2, identified by endothelial protein C receptor (EPCR) expression and absence of CD150, exhibits deeper dormancy and reduced cell cycle activation under inflammatory stress compared to conventional LT-HSCs.

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Key points

  • A novel LT-HSC subset (LT-HSC2) is defined by EPCR expression and CD150 negativity.
  • LT-HSC2s are more deeply dormant than conventional EPCR+CD150+ LT-HSC1s.
  • LT-HSC2s show reduced cell cycle activation in response to inflammatory stress.
  • EPCR and CD150 markers can resolve early lineage divergence trajectories.

AI-generated from the title and abstract; the full text is not read.

Abstract

Cell surface expression of the Slam family member CD150 is widely used for the prospective isolation of multipotent long-term hematopoietic stem cells (LT-HSCs). Here, we identify a bona fide endothelial protein C receptor (EPCR) + CD150 − HSC subset, termed LT-HSC2, that sustains serial multi-lineage reconstitution. Long-term label-retaining assays reveal that LT-HSC2s are more deeply dormant than conventional EPCR + CD150 + LT-HSC1s, exhibit reduced cell cycle activation in response to inflammatory stress, and preserve stemness for prolonged periods in vivo . Moreover, combining EPCR with established HSC and multipotent progenitor (MPP) markers resolves the earliest stages of lineage divergence toward megakaryocytic/erythroid-biased CD150 + and lymphoid-biased CD150 − trajectories. Thus, EPCR expression in HSCs and MPPs is associated with increased stemness, whereas CD150 expression does not encompass the full spectrum of long-term repopulating HSCs. Our findings establish EPCR + CD150 − LT-HSC2s as a distinct, exceptionally dormant stem-cell subset and reveal an additional layer of HSC heterogeneity governing self-renewal, decreased stress sensitvity. and earliest lineage priming.

The authors' abstract, as published at the source. Cell stem cell, 2026 · DOI ↗

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Field: Hematology

HematologyMedicine