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Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt
Abstract
We consider some of the problems involved in current discussions on stem cells in adult mammalian tissues. The present concepts involve a number of pitfalls, weaknesses and logical, semantic and classification problems. This indicates the necessity for new and well-defined concepts that are amenable to experimental analysis. One of the major difficulties in considering stem cells is that they are defined in terms of their functional capabilities which can only be assessed by testing the abilities of the cells, which itself may alter their characteristics during the assay procedure: a situation similar to the uncertainty principle in physics. The terms that describe stem cell functions are often not well defined and are used loosely, which can lead to confusion. If such context-dependent interactions exist between the manipulation and measurement process and the challenged stem cells, the question of, for example, the number of stem cells, in a tissue has to be posed in a new way. Rather than obtaining a single number one might end up with various different numbers under different circumstances, all being complementary. This might suggest that stemness is not a property but a spectrum of capabilities from which to choose. This concept might facilitate a reconciliation between the different and sometimes opposing experimental results. Given certain experimental evidence, we have attempted to provide a novel concept to describe structured cell populations in tissues involving stem cells, transit cells and mature cells. It is based on the primary assumption that the proliferation and differentiation/maturation processes are in principle independent entities in the sense that each may proceed without necessarily affecting the other. Stem cells may divide without maturation while cells approaching functional competence may mature but do not divide. In contrast, transit cells divide and mature showing intermediate properties between stem cells and mature functional cells. The need to describe this transition process and the variable coupling between proliferation and maturation leads us to formulate a spiral model of cell and tissue organisation. This concept is illustrated for the intestinal epithelium. It is concluded that the small intestinal crypts contain 4–16 actual stem cells in steady state but up to 30–40 potential stem cells (clonogenic cells) which may take over stem cell properties following perturbations. This implies that transit cells can under certain circumstances behave like actual stem cells while they undergo maturation under other conditions. There is also evidence that the proliferation and differentiation/maturation processes are subject to controls that ultimately lead to a change in the spiral trajectories.(ABSTRACT TRUNCATED AT 400 WORDS)
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Cites
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., & Stein, H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.4.1710 · Cited by 4,173
Cited by
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539
The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells
van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.-P., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01014-0 · Cited by 2,030
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Astrocytes give rise to new neurons in the adult mammalian hippocampus
Seri, B., Garcı́a-Verdugo, J. M., McEwen, B. S., & Alvarez-Buylla, A. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-18-07153.2001 · Cited by 1,495
Caught up in a Wnt storm: Wnt signaling in cancer
Giles, R. H., van Es, J. H., & Clevers, H. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(03)00005-2 · Cited by 1,482
Morshead, C. M., Reynolds, B. A., Craig, C. G., McBurney, M. W., Staines, W. A., Morassutti, D., Weiss, S., & van der Kooy, D. (1994) · Neuron · doi:10.1016/0896-6273(94)90046-9 · Cited by 1,403
Batlle, E., Henderson, J. T., Beghtel, H., van den Born, M. M. W., Sancho, E., Huls, G., Meeldijk, J., Robertson, J., van de Wetering, M., Pawson, T., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01015-2 · Cited by 1,120
Retinal Stem Cells in the Adult Mammalian Eye
Tropepe, V., Coles, B. L. K., Chiasson, B. J., Horsford, D. J., Elia, A. J., McInnes, R. R., & van der Kooy, D. (2000) · Science · doi:10.1126/science.287.5460.2032 · Cited by 1,081
EGF Converts Transit-Amplifying Neurogenic Precursors in the Adult Brain into Multipotent Stem Cells
Doetsch, F., Petreanu, L., Caille, I., Garcia-Verdugo, J.-M., & Alvarez-Buylla, A. (2002) · Neuron · doi:10.1016/s0896-6273(02)01133-9 · Cited by 1,047
Vescovi, A. L., Galli, R., & Reynolds, B. A. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1889 · Cited by 990
Ding, D.-C., Shyu, W.-C., & Lin, S.-Z. (2011) · Cell Transplantation · doi:10.3727/096368910x · Cited by 894
Minguell, J. J., Erices, A., & Conget, P. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020122600603 · Cited by 871
Niche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem Cell
Conti, L., Pollard, S. M., Gorba, T., Reitano, E., Toselli, M., Biella, G., Sun, Y., Sanzone, S., Ying, Q.-L., Cattaneo, E., et al. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030283 · Cited by 870
Emergent patterns of growth controlled by multicellular form and mechanics
Nelson, C. M., Jean, R. P., Tan, J. L., Liu, W. F., Sniadecki, N. J., Spector, A. A., & Chen, C. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502575102 · Cited by 853
c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation
Wilson, A., Murphy, M. J., Oskarsson, T., Kaloulis, K., Bettess, M. D., Oser, G. M., Pasche, A.-C., Knabenhans, C., MacDonald, H. R., & Trumpp, A. (2004) · Genes & Development · doi:10.1101/gad.313104 · Cited by 823
Intestinal label-retaining cells are secretory precursors expressing Lgr5
Buczacki, S. J. A., Zecchini, H. I., Nicholson, A. M., Russell, R., Vermeulen, L., Kemp, R., & Winton, D. J. (2013) · Nature · doi:10.1038/nature11965 · Cited by 761
Pellegrini, G., Golisano, O., Paterna, P., Lambiase, A., Bonini, S., Rama, P., & De Luca, M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.4.769 · Cited by 722
Xie, T., & Spradling, A. C. (1998) · Cell · doi:10.1016/s0092-8674(00)81424-5 · Cited by 668
Falk, P. G., Hooper, L. V., Midtvedt, T., & Gordon, J. I. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.4.1157-1170.1998 · Cited by 657
Barton, M. K., & Poethig, R. S. (1993) · Development · doi:10.1242/dev.119.3.823 · Cited by 626
Stem Cells and Their Progeny Respond to Nutritional Changes during Drosophila Oogenesis
Drummond-Barbosa, D., & Spradling, A. C. (2001) · Developmental Biology · doi:10.1006/dbio.2000.0135 · Cited by 624
Grandel, H., Kaslin, J., Ganz, J., Wenzel, I., & Brand, M. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.03.040 · Cited by 598
The intestinal epithelial stem cell
Marshman, E., Booth, C., & Potten, C. S. (2002) · BioEssays · doi:10.1002/bies.10028 · Cited by 586
Self-citationNumbers, time and neocortical neuronogenesis: a general developmental and evolutionary model
Caviness, V. S., Takahashi, T., & Nowakowski, R. S. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93933-o · Cited by 567
SIGNALING PATHWAYS IN INTESTINAL DEVELOPMENT AND CANCER
Sancho, E., Batlle, E., & Clevers, H. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.092805 · Cited by 532
Strategies for Homeostatic Stem Cell Self-Renewal in Adult Tissues
Simons, B. D., & Clevers, H. (2011) · Cell · doi:10.1016/j.cell.2011.05.033 · Cited by 489
Identification of a putative intestinal stem cell and early lineage marker; musashi-1
Potten, C. S., Booth, C., Tudor, G. L., Booth, D., Brady, G., Hurley, P., Ashton, G., Clarke, R., Sakakibara, S.-I., & Okano, H. (2003) · Differentiation · doi:10.1046/j.1432-0436.2003.700603.x · Cited by 462
Self-citationMichel, M., Torok, N., Godbout, M. J., Lussier, M., Gaudreau, P., Royal, A., & Germain, L. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.5.1017 · Cited by 441
Nakagawa, T., Nabeshima, Y.-I., & Yoshida, S. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.01.002 · Cited by 398
Uterine stem cells: What is the evidence?
Gargett, C. E. (2007) · Human Reproduction Update · doi:10.1093/humupd/dml045 · Cited by 373
Stem and progenitor cells: the premature desertion of rigorous definitions
Seaberg, R. M., & van der Kooy, D. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00031-6 · Cited by 371
Ye, H., Kelly, T. F., Samadani, U., Lim, L., Rubio, S., Overdier, D. G., Roebuck, K. A., & Costa, R. H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1626 · Cited by 359
Enrichment for murine keratinocyte stem cells based on cell surface phenotype
Tani, H., Morris, R. J., & Kaur, P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.20.10960 · Cited by 355
Periodontal ligament cell populations: The central role of fibroblasts in creating a unique tissue
Lekic, P., & McCulloch, C. A. G. (1996) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199606)245:2<327::aid-ar15>3.0.co;2-r · Cited by 344
Corneal epithelial stem cells at the limbus: looking at some old problems from a new angle
Lavker, R. M., Tseng, S. C. G., & Sun, T.-T. (2004) · Experimental Eye Research · doi:10.1016/j.exer.2003.09.008 · Cited by 339
Schleh, C., Semmler-Behnke, M., Lipka, J., Wenk, A., Hirn, S., Schäffler, M., Schmid, G., Simon, U., & Kreyling, W. G. (2012) · Nanotoxicology · doi:10.3109/17435390.2011.552811 · Cited by 325
Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation
Wong, K.-K., Chang, S., Weiler, S. R., Ganesan, S., Chaudhuri, J., Zhu, C., Artandi, S. E., Rudolph, K. L., Gottlieb, G. J., Chin, L., et al. (2000) · Nature Genetics · doi:10.1038/79232 · Cited by 309
Origin and Structural Evolution of the Early Proliferating Oval Cells in Rat Liver
Paku, S., Schnur, J., Nagy, P., & Thorgeirsson, S. S. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64082-5 · Cited by 286
Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer
Johnston, M. D., Edwards, C. M., Bodmer, W. F., Maini, P. K., & Chapman, S. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611179104 · Cited by 279
A Comprehensive Study of the Radiobiological Response of the Murine (BDF1) Small Intestine
Potten, C. S. (1990) · International Journal of Radiation Biology · doi:10.1080/09553009014552281 · Cited by 272
Self-citationStem cells: the intestinal stem cell as a paradigm
Bach, S. P., Renehan, A. G., & Potten, C. S. (2000) · Carcinogenesis · doi:10.1093/carcin/21.3.469 · Cited by 236
Self-citationThe c‐myc Promoter: Still MysterY and Challenge
(2008) · Advances in Cancer Research · doi:10.1016/s0065-230x(07)99004-1 · Cited by 211
Dynamic Changes in Mouse Hematopoietic Stem Cell Numbers During Aging
de Haan, G., & Van Zant, G. (1999) · Blood · doi:10.1182/blood.v93.10.3294.410k07_3294_3301 · Cited by 208
Gordon, G. J., Coleman, W. B., Hixson, D. C., & Grisham, J. W. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64765-7 · Cited by 187
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Van Leeuwen, I. M. M., Mirams, G. R., Walter, A., Fletcher, A., Murray, P., Osborne, J., Varma, S., Young, S. J., Cooper, J., Doyle, B., et al. (2009) · Cell Proliferation · doi:10.1111/j.1365-2184.2009.00627.x · Cited by 159
Li, L., Liu, L., Rao, J. N., Esmaili, A., Strauch, E. D., Bass, B. L., & Wang, J. (2002) · Gastroenterology · doi:10.1053/gast.2002.35386 · Cited by 91
Guo, J., Longshore, S., Nair, R., & Warner, B. W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806133200 · Cited by 64
Vidrich, A., Buzan, J. M., Brodrick, B., Ilo, C., Bradley, L., Fendig, K. S., Sturgill, T., & Cohn, S. M. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90589.2008 · Cited by 54
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Metadata
- Authors
- Potten, C. S., & Loeffler, M.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1990-12-01
- Volume
- 110
- Issue
- 4
- Pages
- 1001-1020
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2148459495
- Cited by
- 1,791
- References
- 1
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- closed
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