The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
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.
Overview
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.
Integrity signals
Registry
Cites
Statistics
Verification
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.
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?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168
Purification and Characterization of Mouse Hematopoietic Stem Cells
Spangrude, G. J., Heimfeld, S., & Weissman, I. L. (1988) · Science · doi:10.1126/science.2898810 · Cited by 2,908
Self-citationThe bone marrow niche for haematopoietic stem cells
Morrison, S. J., & Scadden, D. T. (2014) · Nature · doi:10.1038/nature12984 · Cited by 2,451
Long-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
Osawa, M., Hanada, K., Hamada, H., & Nakauchi, H. (1996) · Science · doi:10.1126/science.273.5272.242 · Cited by 2,141
Self-citationCD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis
Jaiswal, S., Jamieson, C. H. M., Pang, W. W., Park, C. Y., Chao, M. P., Majeti, R., Traver, D. J., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.046 · Cited by 1,578
Self-citationWhole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis
Susaki, E. A., Tainaka, K., Perrin, D., Kishino, F., Tawara, T., Watanabe, T. M., Yokoyama, C., Onoe, H., Eguchi, M., Yamaguchi, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.042 · Cited by 1,352
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175
Morrison, S. J., & Weissman, I. L. (1994) · Immunity · doi:10.1016/1074-7613(94)90037-x · Cited by 1,116
Self-citationPten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,113
Physiological Migration of Hematopoietic Stem and Progenitor Cells
Wright, D. E., Wagers, A. J., Gulati, A. P., Johnson, F. L., & Weissman, I. L. (2001) · Science · doi:10.1126/science.1064081 · Cited by 933
Self-citationChristensen, J. L., & Weissman, I. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261562798 · Cited by 786
Self-citationIdentification and Specification of the Mouse Skeletal Stem Cell
Chan, C. K. F., Seo, E. Y., Chen, J. Y., Lo, D. D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T. L., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.002 · Cited by 763
Self-citationYamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K. L., Ema, H., & Nakauchi, H. (2013) · Cell · doi:10.1016/j.cell.2013.08.007 · Cited by 745
Self-citationDeep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal
Acar, M., Kocherlakota, K. S., Murphy, M. M., Peyer, J. G., Oguro, H., Inra, C. N., Jaiyeola, C., Zhao, Z., Luby‐Phelps, K., & Morrison, S. J. (2015) · Nature · doi:10.1038/nature15250 · Cited by 729
Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000834107 · Cited by 711
Self-citationOguro, H., Ding, L., & Morrison, S. J. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.05.014 · Cited by 692
Passegué, E., Wagers, A. J., Giuriato, S., Anderson, W. C., & Weissman, I. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050967 · Cited by 646
Self-citationA transcription activator-like effector toolbox for genome engineering
Sanjana, N. E., Cong, L., Zhou, Y., Cunniff, M. M., Feng, G., & Zhang, F. (2012) · Nature Protocols · doi:10.1038/nprot.2011.431 · Cited by 643
Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632
Interpreting flow cytometry data: a guide for the perplexed
Herzenberg, L. A., Tung, J., Moore, W. A., Herzenberg, L. A., & Parks, D. R. (2006) · Nature Immunology · doi:10.1038/ni0706-681 · Cited by 464
Lu, R., Neff, N. F., Quake, S. R., & Weissman, I. L. (2011) · Nature Biotechnology · doi:10.1038/nbt.1977 · Cited by 451
Self-citationUchida, N., & Weissman, I. L. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.1.175 · Cited by 359
Self-citationFunctional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells
Fleming, W., Alpern, E., Uchida, N., Ikuta, K., Spangrude, G. J., & Weissman, I. L. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.4.897 · Cited by 277
Self-citationGene Expression Commons: An Open Platform for Absolute Gene Expression Profiling
Seita, J., Sahoo, D., Rossi, D. J., Bhattacharya, D., Serwold, T. F., Inlay, M. A., Ehrlich, L. I. R., Fathman, J. W., Dill, D. L., & Weissman, I. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040321 · Cited by 258
Self-citationMulti-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation
Guo, W., Lasky, J. L., Chang, C.-J., Mosessian, S., Lewis, X., Xiao, Y., Yeh, J., Chen, J. Y., Iruela‐Arispe, M. L., Varella‐Garcia, M., et al. (2008) · Nature · doi:10.1038/nature06933 · Cited by 246
Self-citationFgd5 identifies hematopoietic stem cells in the murine bone marrow
Gazit, R., Mandal, P. K., Ebina, W., Ben‐Zvi, A., Nombela‐Arrieta, C., Silberstein, L. E., & Rossi, D. J. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20130428 · Cited by 201
Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands
Moraga, I., Wernig, G., Wilmes, S., Gryshkova, V., Richter, C. P., Hong, W., Sinha, R., Guo, F., Fabionar, H., Wehrman, T. S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.011 · Cited by 173
Self-citationClonal precursor of bone, cartilage, and hematopoietic niche stromal cells
Chan, C. K. F., Lindau, P., Jiang, W., Chen, J. Y., Zhang, L. F., Chen, C., Seita, J., Sahoo, D., Kim, J., Lee, A. S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310212110 · Cited by 134
Self-citationMolecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells
Forsberg, E. C., Passegué, E., Prohaska, S. S., Wagers, A. J., Koeva, M., Stuart, J. M., & Weissman, I. L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008785 · Cited by 127
Self-citationOLego: fast and sensitive mapping of spliced mRNA-Seq reads using small seeds
Wu, J., Anczuków, O., Krainer, A. R., Zhang, M. Q., & Zhang, C. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt216 · Cited by 123
Hosen, N., Yamane, T., Muijtjens, M., Pham, K., Clarke, M. F., & Weissman, I. L. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0229 · Cited by 106
Self-citationHills, D., Gribi, R., Ure, J. M., Buza-Vidas, N., Luc, S., Jacobsen, S. E. W., & Medvinsky, A. (2011) · Blood · doi:10.1182/blood-2009-12-253989 · Cited by 32
Fathman, J. W., Fernhoff, N. B., Seita, J., Chao, C., Scarfone, V. M., Weissman, I. L., & Inlay, M. A. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.09.007 · Cited by 25
Self-citation
Cited by
Sorted by citations
Single-cell transcriptional diversity is a hallmark of developmental potential
Gulati, G. S., Sikandar, S. S., Wesche, D. J., Manjunath, A., Bharadwaj, A., Berger, M. J., Ilagan, F., Kuo, A. H., Hsieh, R. W., Cai, S., et al. (2020) · Science · doi:10.1126/science.aax0249 · Cited by 1,571
Haematopoietic stem cell activity and interactions with the niche
Pinho, S., & Frenette, P. S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0103-9 · Cited by 1,064
A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation
Nestorowa, S., Hamey, F. K., Pijuan Sala, B., Diamanti, E., Shepherd, M., Laurenti, E., Wilson, N. K., Kent, D. G., & Göttgens, B. (2016) · Blood · doi:10.1182/blood-2016-05-716480 · Cited by 768
Adult haematopoietic stem cell niches
Crane, G. M., Jeffery, E., & Morrison, S. J. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.53 · Cited by 712
Tissue clearing and its applications in neuroscience
Ueda, H. R., Ertürk, A., Chung, K., Gradinaru, V., Chédotal, A., Tomančák, P., & Keller, P. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0250-1 · Cited by 650
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
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
