The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Open accessAbstract
A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult 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
“Upregulation of p16 and Arf has been implicated in mediating the induction of cellular senescence in a variety of cells including HSCs.”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [15]
In the citing paper
“However, it appears that p16, but not Arf, plays an important role in mediating induction of Bmi1−/− HSC senescence, whereas Arf mainly promotes HSC apoptosis.15”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [15]
In the citing paper
“For example, increased expression of p16 and Arf was found in HSCs from Bmi1−/− mice.15”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [15]
In the citing paper
“ROS plays an important role in mediating induction of HSC senescence under various pathological conditions, such as mutation of ATM and various Fanconi anemia genes; deletion of Bmi1, FoxOs, Mdm2, and Tsc1; and aging.15,19,20,35-38”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [15]
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
Production of high-titer helper-free retroviruses by transient transfection.
Pear, W. S., Nolan, G. P., Scott, M. L., & Baltimore, D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8392 · Cited by 2,267
"Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells
Ramalho‐Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C., & Melton, D. A. (2002) · Science · doi:10.1126/science.1072530 · Cited by 1,711
Zhang, Y., Xiong, Y., & Yarbrough, W. G. (1998) · Cell · doi:10.1016/s0092-8674(00)81401-4 · Cited by 1,626
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Ouelle, D. E., Zindy, F., Ashmun, R. A., & Sherr, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90214-7 · Cited by 1,485
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Lessard, J., & Sauvageau, G. (2003) · Nature · doi:10.1038/nature01572 · Cited by 1,452
Hematopoietic Stem Cell Quiescence Maintained by p21 cip1/waf1
Cheng, T., Rodrigues, N., Shen, H., Yang, Y.-G., Dombkowski, D., Sykes, M., & Scadden, D. T. (2000) · Science · doi:10.1126/science.287.5459.1804 · Cited by 1,339
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206 · cited 1×
“Analysis of genes expressed in HSCs identified Bmi-1 , a member of the Polycomb Group ( PcG ) family linked to malignant transformation, lymphocyte development, neurological development and senescence of fibroblast”
BackgroundMorrison, S. J., & Weissman, I. L. (1994) · Immunity · doi:10.1016/1074-7613(94)90037-x · Cited by 1,116
Self-citationNucleolar Arf sequesters Mdm2 and activates p53
Weber, J. D., Taylor, L. J., Roussel, M. F., Sherr, C. J., & Bar-Sagi, D. (1999) · Nature Cell Biology · doi:10.1038/8991 · Cited by 940
Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL
Shivdasani, R. A., Mayer, E. L., & Orkin, S. H. (1995) · Nature · doi:10.1038/373432a0 · Cited by 938
Christensen, J. L., & Weissman, I. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261562798 · Cited by 786
Self-citationvan der Lugt, N. M. T., Domen, J., Linders, K., van ROON, M. A., Robanus-Maandag, E. C., Riele, H. T., van der Valk, M., Deschamps, J., Sofroniew, M. V., & van Lohuizen, M. (1994) · Genes & Development · doi:10.1101/gad.8.7.757 · Cited by 781
The T Cell Leukemia Oncoprotein SCL/tal-1 Is Essential for Development of All Hematopoietic Lineages
Porcher, C., Swat, W., Rockwell, K. R., Fujiwara, Y., Alt, F. W., & Orkin, S. H. (1996) · Cell · doi:10.1016/s0092-8674(00)80076-8 · Cited by 731
HOXB4-Induced Expansion of Adult Hematopoietic Stem Cells Ex Vivo
Antonchuk, J., Sauvageau, G., & Humphries, R. K. (2002) · Cell · doi:10.1016/s0092-8674(02)00697-9 · Cited by 700
The purification and characterization of fetal liver hematopoietic stem cells
Morrison, S. J., Hemmati, H. D., Wandycz, A. M., & Weissman, I. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.22.10302 · Cited by 611
Self-citationHematopoietic Stem Cells Are Uniquely Selective in Their Migratory Response to Chemokines
Wright, D. E., Bowman, E. P., Wagers, A. J., Butcher, E. C., & Weissman, I. L. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011284 · Cited by 514
Self-citationAkashi, K., He, X., Chen, J., Iwasaki, H., Niu, C. S., Steenhard, B. M., Zhang, J., Haug, J., & Li, L. (2002) · Blood · doi:10.1182/blood-2002-06-1780 · Cited by 368
The Role of Apoptosis in the Regulation of Hematopoietic Stem Cells
Domen, J., Cheshier, S. H., & Weissman, I. L. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.2.253 · Cited by 332
Self-citationLawrence, H. J., Helgason, C. D., Sauvageau, G., Fong, S., Izon, D. J., Humphries, R. K., & Largman, C. (1997) · Blood · doi:10.1182/blood.v89.6.1922 · Cited by 303
Defects in Hemopoietic Stem Cell Activity in Ikaros Mutant Mice
Nichogiannopoulou, A., Trevisan, M., Neben, S., Friedrich, C., & Georgopoulos, K. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.9.1201 · Cited by 232
Antonchuk, J., Sauvageau, G., & Humphries, R. K. (2001) · Experimental Hematology · doi:10.1016/s0301-472x(01)00681-6 · Cited by 221
Polycomb Group Gene rae28 Is Required for Sustaining Activity of Hematopoietic Stem Cells
Ohta, H., Sawada, A., Kim, J. Y., Tokimasa, S., Nishiguchi, S., Humphries, R. K., Hara, J., & Takihara, Y. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011911 · Cited by 183
Differential gene expression profiling of adult murine hematopoietic stem cells
Park, I.-K., He, Y., Lin, F., Lærum, O. D., Tian, Q., Bumgarner, R. E., Klug, C. A., Li, K., Kuhr, C. S., Doyle, M. J., et al. (2002) · Blood · doi:10.1182/blood.v99.2.488 · Cited by 171
Self-citationStage-Specific Expression of Polycomb Group Genes in Human Bone Marrow Cells
Lessard, J. A., Baban, S., & Sauvageau, G. (1998) · Blood · doi:10.1182/blood.v91.4.1216 · Cited by 162
The Polycomb-group homolog Bmi-1 is a regulator of murine Hox gene expression
van der Lugt, N. M. T., Alkema, M. J., Berns, A. J. M., & Deschamps, J. (1996) · Mechanisms of Development · doi:10.1016/s0925-4773(96)00570-9 · Cited by 134
Chromatin silencing and activation by Polycomb and trithorax group proteins
Mahmoudi, T., & Verrijzer, C. P. (2001) · Oncogene · doi:10.1038/sj.onc.1204330 · Cited by 134
Park, I.-K., Klug, C. A., Li, K., Jerabek, L., Li, L., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., & Clarke, M. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005947200 · Cited by 58
Self-citationFisher, R. C., Lovelock, J. D., & Scott, E. W. (1999) · Blood · doi:10.1182/blood.v94.4.1283 · Cited by 51
Retroviral Transduction of FACS-Purified Hematopoietic Stem Cells
Cotta, C. V., Swindle, C. S., Weissman, I. L., & Klug, C. A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-140-x:243 · Cited by 2
Self-citation
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Lee, J., Kotliarova, S. E., Kotliarov, Y., Li, A., Su, Q., Donin, N. M., Pastorino, S., Purow, B. W., Christopher, N., Zhang, W., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.030 · Cited by 2,345
Evolution of the Cancer Stem Cell Model
Kreso, A., & Dick, J. E. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.006 · Cited by 2,304
Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P. D., Weissman, I. L., Clarke, M. F., & Ailles, L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610117104 · Cited by 2,205
Self-citationCancerous stem cells can arise from pediatric brain tumors
Hemmati, H. D., Nakano, I., Lazareff, J. A., Masterman-Smith, M. D., Geschwind, D. H., Bronner-Fraser, M. E., & Kornblum, H. I. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2036535100 · Cited by 1,842
The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs
Wellner, U. F., Schubert, J., Burk, U., Schmalhofer, O., Zhu, F., Sonntag, A., Waldvogel, B., Vannier, C., Darling, D. S., Hausen, A. Z., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1998 · Cited by 1,733
Metadata
- Authors
- Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F.
- Affiliations
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Stanford Medicine (US)
- Corresponding author
- Clarke, Michael F.
- ORCID
- Venue
- Nature
- Published
- 2003-04-20
- Volume
- 423
- Issue
- 6937
- Pages
- 302-305
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2021050536
- Cited by
- 1,871
- References
- 31
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 15 · 2023: 29 · 2022: 50 · 2021: 48 · 2020: 45 · 2019: 51 · 2018: 52 · 2017: 68 · 2016: 79 · 2015: 81 · 2014: 97 · 2013: 100 · 2012: 127
- FWCI
- 55.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- 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
- BMI1, hematopoietic stem cells, self-renewal, stem cell maintenance, p16INK4a, p19ARF, p53-dependent cell death, growth arrest, cell survival genes, hematopoiesis, bone marrow
- MeSH terms
- Proto-Oncogene Mas, Animals, Bone Marrow Cells, Cell Division, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Liver, Models, Biological, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, RNA, Messenger, Bone Marrow Transplantation, Gene Deletion, Hematopoietic Stem Cell Transplantation, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Protein p14ARF, Mice, Polycomb Repressive Complex 1
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
