Cited by 49Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

CD34 and EPCR coordinately enrich functional murine hematopoietic stem cells under normal and inflammatory conditions

Open access
Rabe, Jennifer L., Hernandez, Giovanny, Chavez, James S., Mills, Taylor S., Nerlov, Claus, Pietras, Eric M.·2020·Experimental Hematology

Abstract

Hematopoiesis is dynamically regulated to maintain blood system function under nonhomeostatic conditions such as inflammation and injury. However, common surface marker and hematopoietic stem cell (HSC) reporter systems used for prospective enrichment of HSCs have been less rigorously tested in these contexts. Here, we use two surface markers, EPCR/CD201 and CD34, to re-analyze dynamic changes in the HSC-enriched phenotypic SLAM compartment in a mouse model of chronic interleukin (IL)-1 exposure. EPCR and CD34 coordinately identify four functionally and molecularly distinct compartments within the SLAM fraction, including an EPCR+/CD34- fraction whose long-term serial repopulating activity is only modestly impacted by chronic IL-1 exposure, relative to unfractionated SLAM cells. Notably, the other three fractions expand in frequency following IL-1 treatment and represent actively proliferating, lineage-primed cell states with limited long-term repopulating potential. Importantly, we find that the Fgd5-ZSGreen HSC reporter mouse enriches for molecularly and functionally intact HSCs regardless of IL-1 exposure. Together, our findings provide further evidence of dynamic heterogeneity within a commonly used HSC-enriched phenotypic compartment under stress conditions. Importantly, they also indicate that stringency of prospective isolation approaches can enhance interpretation of findings related to HSC function when studying models of hematopoietic stress.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.exphem.2019.12.003

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increased PU.1 expression triggers enhanced activation of myeloid differentiation pathways in HSPC, leading to increased myeloid cell output, sometimes referred to as myeloid-biased hematopoiesis.

    “Increased PU.1 expression in turn triggers enhanced activation of myeloid differentiation pathways in HSPC, leading to increased myeloid cell output, sometimes referred to as “myeloid-biased” hematopoiesis (Pietras et al., 2016; Rabe et al., 2020; Ahmed et al., 2022; Chavez et al., 2022).”

    From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Rabe et al., 2020

    The Results sections on EPCR/CD34 enrichment and lineage priming (page unavailable) report that chronic IL-1 exposure expanded bone-marrow myeloid cells and increased expression of Spi1/Pu.1, a myeloid lineage determinant, in an HSC-enriched fraction. They do not establish that increased PU.1 itself activates myeloid differentiation pathways or causes the increased myeloid output. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • The findings imply the existence of a braking mechanism that limits HSC cell cycle entry in response to chronic inflammatory stress.

    “These findings imply the existence of a braking mechanism that limits HSC cell cycle entry in response to chronic inflammatory stress (Pietras et al., 2016; Rabe et al., 2020).”
  • IL-1β treatment for 20 d in mice models chronic inflammatory stress.

    “isolated from the BM of mice treated with or without IL-1β for 20 d to model chronic inflammatory stress (Fig. 1 A; Pietras et al., 2016; Rabe et al., 2020).”
  • HSCLT-enriched SLAM cells overlap phenotypically with deeply quiescent CD49blo reserve HSCs and remain almost exclusively in a quiescent (G0) cell cycle state despite chronic IL-1 exposure.

    “We previously showed that HSCLT-enriched SLAM cells (defined as LSK/Flk2−CD48−CD150+CD34−EPCR+; Fig. S1 E) overlap phenotypically with deeply quiescent CD49blo reserve HSCs (Zhao et al., 2019) and remain almost exclusively in a quiescent (G0) cell cycle state, despite chronic IL-1 exposure (Rabe et al., 2020).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Rabe, J. L., Hernandez, G., Chavez, J. S., Mills, T. S., Nerlov, C., & Pietras, E. M.
Affiliations
  • University of Colorado Anschutz (US)
  • University of Oxford (GB)
Corresponding author
Pietras, Eric M.
Venue
Experimental Hematology
Publisher
Elsevier BV
Published
2020-01
Volume
81
Pages
1-15.e6
ISSN
0301-472X (ISSN-L)
OpenAlex
W2995196097
Cited by
49
References
63
Citations by year
2026: 9 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 13 · 2021: 10 · 2020: 4
FWCI
4.77
Type
journal article
Language
en
Open access
Locations
  • Experimental Hematology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
hematopoietic stem cells, CD34, endothelial protein C receptor, SLAM family receptors, inflammation, HSC heterogeneity, HSC isolation, hematopoietic stress
MeSH terms
Endothelial Protein C Receptor, Animals, Hematopoiesis, Hematopoietic Stem Cells, Inflammation, Interleukin-1, Mice, Transgenic, Stress, Physiological, Antigens, CD34, Cell Proliferation, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review