Cited by 345Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche

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Abstract

Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs.

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Crossref · 10.1038/nature16943

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  • A distinct valley in RNA abundance coincided with elevated expression of Hoxb5, a marker of long-term or quiescent HSCs.

    “By devising a simple approach to visualize inferred RNA content as a function of CytoTRACE (Fig. 3D, top), we observed a distinct valley in RNA abundance that coincided with elevated expression of Hoxb5, a marker of long-term or quiescent HSCs (35) (Fig. 3D, bottom).”

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Authors
Chen, J. Y., Miyanishi, M., Wang, S. K., Yamazaki, S., Sinha, R., Kao, K. S., Seita, J., Sahoo, D., Nakauchi, H., & Weissman, I. L.
Affiliations
  • Stanford Medicine (US)
  • Institute of Medical Science, The University of Tokyo (JP)
  • Institute for Stem Cell Biology and Regenerative Medicine (US)
Corresponding author
  • Miyanishi, Masanori
  • Weissman, Irving L.
Venue
Nature
Published
2016-02
Volume
530
Issue
7589
Pages
223-227
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2261428502
Cited by
345
References
34
Citations by year
2026: 9 · 2025: 23 · 2024: 25 · 2023: 23 · 2022: 34 · 2021: 48 · 2020: 38 · 2019: 35 · 2018: 39 · 2017: 45 · 2016: 25
FWCI
45.68
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Japan Society for the Promotion of Science (25640044, 16H02661)
  • National Heart, Lung, and Blood Institute (R01HL058770, F30HL122096, U01HL099999)
  • National Cancer Institute (R00CA151673, R01CA086065)
  • National Institute of General Medical Sciences (T32GM007365)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Blood disorders and treatments
Keywords
HOXB5, hematopoietic stem cells, perivascular niche, endothelial cells, VE-cadherin, HSC niche, HSC self-renewal, bone marrow
MeSH terms
Cell Self Renewal, Cadherin 5, Animals, Bone Marrow, Gene Expression Regulation, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Biomarkers, Antigens, CD, Cadherins, Immunophenotyping, Genes, Reporter, Hematopoietic Stem Cell Transplantation, Homeodomain Proteins, Mice, Stem Cell Niche

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