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Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche
Open accessAbstract
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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“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).”
From Single-cell transcriptional diversity is a hallmark of developmental potential (2020) · cites this paper as [35]
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Metadata
- 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.
- ORCID
- Venue
- Nature
- Published
- 2016-02
- Volume
- 530
- Issue
- 7589
- Pages
- 223-227
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4854608
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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