The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Molecular Signatures of Proliferation and Quiescence in Hematopoietic Stem Cells
Open accessAbstract
Stem cells resident in adult tissues are principally quiescent, yet harbor enormous capacity for proliferation to achieve self renewal and to replenish their tissue constituents. Although a single hematopoietic stem cell (HSC) can generate sufficient primitive progeny to repopulate many recipients, little is known about the molecular mechanisms that maintain their potency or regulate their self renewal. Here we have examined the gene expression changes that occur over a time course when HSCs are induced to proliferate and return to quiescence in vivo. These data were compared to data representing differences between naturally proliferating fetal HSCs and their quiescent adult counterparts. Bioinformatic strategies were used to group time-ordered gene expression profiles generated from microarrays into signatures of quiescent and dividing stem cells. A novel method for calculating statistically significant enrichments in Gene Ontology groupings for our gene lists revealed elemental subgroups within the signatures that underlie HSC behavior, and allowed us to build a molecular model of the HSC activation cycle. Initially, quiescent HSCs evince a state of readiness. The proliferative signal induces a preparative state, which is followed by active proliferation divisible into early and late phases. Re-induction of quiescence involves changes in migratory molecule expression, prior to reestablishment of homeostasis. We also identified two genes that increase in both gene and protein expression during activation, and potentially represent new markers for proliferating stem cells. These data will be of use in attempts to recapitulate the HSC self renewal process for therapeutic expansion of stem cells, and our model may correlate with acquisition of self renewal characteristics by cancer stem cells.
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.
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
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
Sherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379
In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells
Cheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858
Levy, D. E., & Lee, C.-K. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215650 · Cited by 734
Qi, J. H., Ebrahem, Q., Moore, N., Murphy, G., Claesson-Welsh, L., Bond, M., Baker, A., & Anand-Apte, B. (2003) · Nature Medicine · doi:10.1038/nm846 · Cited by 658
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
Wright, D. E., Cheshier, S. H., Wagers, A. J., Randall, T. D., Christensen, J. L., & Weissman, I. L. (2001) · Blood · doi:10.1182/blood.v97.8.2278 · Cited by 208
Cited by
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
Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
Malta, T. M., Sokolov, A., Gentles, A. J., Burzykowski, T., Poisson, L., Weinstein, J. N., Kamińska, B., Huelsken, J., Omberg, L., Gevaert, O., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.034 · Cited by 2,180
Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908
Cancer stem cells: an old idea–a paradigm shift
Wicha, M. S., Liu, S., & Dontu, G. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3153 · Cited by 1,378
Dnmt3a is essential for hematopoietic stem cell differentiation
Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122
Self-citationProstaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis
North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., Weber, G. J., Bowman, T. V., Jang, I.-H., Grosser, T., et al. (2007) · Nature · doi:10.1038/nature05883 · Cited by 1,029
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C., & Goodell, M. A. (2010) · Nature · doi:10.1038/nature09135 · Cited by 877
Self-citationSun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686
Self-citationPassegué, 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
Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., DeLeo, A. M., Pastrana, E., & Doetsch, F. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.039 · Cited by 634
p53 Regulates Hematopoietic Stem Cell Quiescence
Liu, Y., Elf, S. E., Miyata, Y., Sashida, G., Liu, Y., Huang, G., Di Giandomenico, S., Lee, J. M., Deblasio, A., Menendez, S., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2008.11.006 · Cited by 547
Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy
Cabezas-Wallscheid, N., Buettner, F., Sommerkamp, P., Klimmeck, D., Ladel, L., Thalheimer, F. B., Pastor-Flores, D., Roma, L. P., Renders, S., Zeisberger, P., et al. (2017) · Cell · doi:10.1016/j.cell.2017.04.018 · Cited by 454
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity
Laurenti, E., Varnum-Finney, B., Wilson, A., Ferrero, I., Blanco-Bose, W. E., Ehninger, A., Knoepfler, P. S., Cheng, P.-F., MacDonald, H. R., Eisenman, R. N., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.09.005 · Cited by 305
Giles, J. R., Ngiow, S. F., Manne, S., Baxter, A. E., Khan, O., Wang, P., Staupe, R., Abdel-Hakeem, M. S., Huang, H., Mathew, D., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01338-4 · Cited by 264
Welner, R. S., Amabile, G., Bararia, D., Czibere, A., Yang, H., Zhang, H., Pontes, L. L. D. F., Ye, M., Levantini, E., Di Ruscio, A., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.004 · Cited by 129
Molecular 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
Dong, F., Hao, S., Zhang, S., Zhu, C., Cheng, H., Yang, Z., Hamey, F. K., Wang, X., Gao, A., Wang, F., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0512-1 · Cited by 121
Tipping, A. J., Pina, C., Castor, A., Hong, D., Rodrigues, N. P., Lazzari, L., May, G. E., Jacobsen, S. E. W., & Enver, T. (2009) · Blood · doi:10.1182/blood-2008-06-161117 · Cited by 116
Lopez, R. G., Garcia-Silva, S., Moore, S. J., Bereshchenko, O., Martinez-Cruz, A. B., Ermakova, O., Kurz, E., Paramio, J. M., & Nerlov, C. (2009) · Nature Cell Biology · doi:10.1038/ncb1960 · Cited by 106
ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation
Knudsen, K. J., Rehn, M., Hasemann, M. S., Rapin, N., Bagger, F. O., Ohlsson, E., Willer, A., Frank, A.-K., Søndergaard, E., Jendholm, J., et al. (2015) · Genes & Development · doi:10.1101/gad.268409.115 · Cited by 98
Freire, P. R., & Conneely, O. M. (2018) · Blood · doi:10.1182/blood-2017-07-795757 · Cited by 70
Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis
Mallaney, C., Ostrander, E. L., Celik, H., Kramer, A. C., Martens, A., Kothari, A., Koh, W. K., Haussler, E., Iwamori, N., Gontarz, P., et al. (2019) · Leukemia · doi:10.1038/s41375-019-0462-4 · Cited by 63
An, N., Khan, S., Imgruet, M. K., Gurbuxani, S. K., Konecki, S. N., Burgess, M. R., & McNerney, M. E. (2018) · Blood · doi:10.1182/blood-2017-10-810028 · Cited by 55
Daria, D., Filippi, M.-D., Knudsen, E. S., Faccio, R., Li, Z., Kalfa, T., & Geiger, H. (2008) · Blood · doi:10.1182/blood-2007-02-071746 · Cited by 46
The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function
Mohr, J., Dash, B. P., Schnoeder, T. M., Wolleschak, D., Herzog, C., Tubio Santamaria, N., Weinert, S., Godavarthy, S., Zanetti, C., Naumann, M., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0025-0 · Cited by 23
Kim, E., Cheng, Y., Bolton-Gillespie, E., Cai, X., Ma, C., Tarangelo, A., Le, L., Jambhekar, M., Raman, P., Hayer, K. E., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20160719 · Cited by 18
Metadata
- Authors
- Venezia, T. A., Merchant, A. A., Ramos, C. A., Whitehouse, N. L., Young, A. S., Shaw, C. A., & Goodell, M. A.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2004-09-28
- Volume
- 2
- Issue
- 10
- Pages
- e301
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2016536941
- Cited by
- 362
- References
- 7
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- gold
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
