Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Abstract
How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment.
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During physiological growth in humans, mice and other species, juvenile β-cells expand by self-renewal while maintaining their hallmark functions.
“During physiological growth in humans, mice and other species, juvenile β-cells expand by self-renewal7,8 while maintaining their hallmark functions.”
From PDGF signalling controls age-dependent proliferation in pancreatic β-cells (2011) · cites this paper as [7]
In young adult mice, most new β-cells come from replication of pre-existing β-cells, and few if any come from progenitors under normal conditions.
“Genetic lineage tracing studies performed in the young adult mouse indicate that the great majority of new β-cells are derived through replication of pre-existing β-cells and few, if any, newly formed β-cells stem from progenitor populations under normal circumstances, at least in rodents [23].”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [23]
New β-cells can arise from proliferation of preexisting β-cells.
“Lineage tracing experiments show that new β-cells can arise from proliferation of preexisting β-cells (8).”
From Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice (2009) · cites this paper as [8]
Normal β-cell growth primarily occurs by self-renewal of mature β-cells-not by replication of specialized progenitors.
“the findings of recent studies by several groups (including ours) indicate that normal β-cell growth primarily occurs by self-renewal of mature β-cells—not by replication of specialized progenitors (8–12).”
From Adaptive β-Cell Proliferation Is Severely Restricted With Advanced Age (2009) · cites this paper as [8]
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Rother, K. I., Spain, L. M., Wesley, R. A., Digon, B. J., Baron, A., Chen, K., Nelson, P., Dosch, H.-M., Palmer, J. P., Brooks-Worrell, B., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0773 · Cited by 133 · see citing works
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Jiao, Y., Le Lay, J., Yu, M., Naji, A., & Kaestner, K. H. (2014) · Diabetes · doi:10.2337/db13-1435 · Cited by 118 · see citing works
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Reers, C., Erbel, S., Esposito, I., Schmied, B., Büchler, M. W., Nawroth, P. P., & Ritzel, R. A. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0596 · Cited by 113 · see citing works
Jin, L., Feng, T., Shih, H. P., Zerda, R., Luo, A., Hsu, J., Mahdavi, A., Sander, M., Tirrell, D. A., Riggs, A. D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301889110 · Cited by 108 · see citing works
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Guo, N., Parry, E. M., Li, L.-S., Kembou, F., Lauder, N., Hussain, M. A., Berggren, P.-O., & Armanios, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017858 · Cited by 100 · see citing works
Zhong, L., Georgia, S., Tschen, S.-I., Nakayama, K., Nakayama, K., & Bhushan, A. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32198 · Cited by 92 · see citing works
Dual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β Cell Growth
Zhu, D., Zhang, Y., Lam, P. P. L., Dolai, S., Liu, Y., Cai, E. P., Choi, D., Schroer, S. A., Kang, Y., Allister, E. M., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.001 · Cited by 87 · see citing works
Klinger, S., Poussin, C., Debril, M.-B., Dolci, W., Halban, P. A., & Thorens, B. (2008) · Diabetes · doi:10.2337/db07-1414 · Cited by 86 · see citing works
Blandino-Rosano, M., Perez-Arana, G., Mellado-Gil, J. M., Segundo, C., & Aguilar-Diosdado, M. (2008) · Journal of Molecular Endocrinology · doi:10.1677/jme-07-0154 · Cited by 82 · see citing works
Osteocalcin effect on human β-cells mass and function
Sabek, O. M., Nishimoto, S. K., Fraga, D., Tejpal, N., Ricordi, C., & Gaber, A. O. (2015) · Endocrinology · doi:10.1210/en.2015-1143 · Cited by 74 · see citing works
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Tavana, O., Puebla-Osorio, N., Sang, M., & Zhu, C. (2010) · Diabetes · doi:10.2337/db09-0792 · Cited by 58 · see citing works
Are there pancreatic progenitor cells from which new islets form after birth?
Bonner-Weir, S., & Sharma, A. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0186 · Cited by 57 · see citing works
Tissue Stem Cells: New Tools and Functional Diversity
Grompe, M. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.006 · Cited by 54 · see citing works
Keefe, M., Wang, H., De La O, J.-P., Khan, A., Firpo, M. A., & Murtaugh, L. C. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.007799 · Cited by 54 · see citing works
Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin
Jiang, Y., Nishimura, W., Devor-Henneman, D., Kusewitt, D., Wang, H., Holloway, M. P., Dohi, T., Sabo, E., Robinson, M. L., Altieri, D. C., et al. (2008) · Diabetes · doi:10.2337/db08-0170 · Cited by 38 · see citing works
Measurement of pancreatic islet cell proliferation by heavy water labeling
Chen, S., Turner, S., Tsang, E., Stark, J., Turner, H., Mahsut, A., Keifer, K., Goldfinger, M., & Hellerstein, M. K. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00375.2007 · Cited by 34 · see citing works
Jin, L., Gao, D., Feng, T., Tremblay, J. R., Ghazalli, N., Luo, A., Rawson, J., Quijano, J. C., Chai, J., Wedeken, L., et al. (2016) · Stem Cell Research · doi:10.1016/j.scr.2015.11.015 · Cited by 32 · see citing works
Scharfmann, R. (2008) · Diabetologia · doi:10.1007/s00125-007-0909-4 · Cited by 9 · see citing works
Horiguchi, M., Yoshida, M., Hirata, K., Furuyama, K., Masui, T., Uemoto, S., & Kawaguchi, Y. (2019) · FEBS Letters · doi:10.1002/1873-3468.13504 · Cited by 7 · see citing works
- Authors
- Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Melton, Douglas A.
- Venue
- Nature
- Published
- 2004-05
- Volume
- 429
- Issue
- 6987
- Pages
- 41-46
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2041739600
- Cited by
- 2,219
- References
- 0
- Citations by year
- 2026: 28 · 2025: 37 · 2024: 39 · 2023: 48 · 2022: 57 · 2021: 61 · 2020: 59 · 2019: 66 · 2018: 71 · 2017: 66 · 2016: 102 · 2015: 128 · 2014: 120 · 2013: 138 · 2012: 124
- FWCI
- 150.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- pancreatic beta cells, beta-cell proliferation, self-replication, adult stem cells, stem cell differentiation, lineage tracing, pancreatic resection, tissue turnover
- MeSH terms
- Aging, Animals, Cell Count, Cell Differentiation, Cell Division, Islets of Langerhans, Mice, Transgenic, Pancreatectomy, Recombination, Genetic, Regeneration, Cell Lineage, Pluripotent Stem Cells, Mice
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