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Colony-forming cells in the adult mouse pancreas are expandable in Matrigel and form endocrine/acinar colonies in laminin hydrogel
Open accessAbstract
The study of hematopoietic colony-forming units using semisolid culture media has greatly advanced the knowledge of hematopoiesis. Here we report that similar methods can be used to study pancreatic colony-forming units. We have developed two pancreatic colony assays that enable quantitative and functional analyses of progenitor-like cells isolated from dissociated adult (2–4 mo old) murine pancreas. We find that a methylcellulose-based semisolid medium containing Matrigel allows growth of duct-like “Ring/Dense” colonies from a rare ( ∼ 1%) population of total pancreatic single cells. With the addition of roof plate-specific spondin 1, a wingless-int agonist, Ring/Dense colony-forming cells can be expanded more than 100,000-fold when serially dissociated and replated in the presence of Matrigel. When cells grown in Matrigel are then transferred to a Matrigel-free semisolid medium with a unique laminin-based hydrogel, some cells grow and differentiate into another type of colony, which we name “Endocrine/Acinar.” These Endocrine/Acinar colonies are comprised mostly of endocrine- and acinar-like cells, as ascertained by RNA expression analysis, immunohistochemistry, and electron microscopy. Most Endocrine/Acinar colonies contain beta-like cells that secrete insulin/C-peptide in response to D -glucose and theophylline. These results demonstrate robust self-renewal and differentiation of adult Ring/Dense colony-forming units in vitro and suggest an approach to producing beta-like cells for cell replacement of type 1 diabetes. The methods described, which include microfluidic expression analysis of single cells and colonies, should also advance study of pancreas development and pancreatic progenitor cells.
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“After 2 weeks, endocrine-acinar organoids were observed, demonstrating that aECM-lam was capable of inducing differentiation of ductal progenitor cells into endocrine and acinar lineages192.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [192]
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Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108
Insulin-promoter-factor 1 is required for pancreas development in mice
Jonsson, J., Carlsson, L., Edlund, T., & Edlund, H. (1994) · Nature · doi:10.1038/371606a0 · Cited by 1,879
Gu, G., Dubauskaite, J., & Melton, D. A. (2002) · Development · doi:10.1242/dev.129.10.2447 · Cited by 1,518
Notch signalling controls pancreatic cell differentiation
Apelqvist, Å., Li, H., Sommer, L., Beatus, P., Anderson, D. J., Honjo, T., de Angelis, M. H., Lendahl, U., & Edlund, H. (1999) · Nature · doi:10.1038/23716 · Cited by 1,158
β Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas
Xu, X., D’Hoker, J., Stangé, G. M., Bonné, S., Leu, N. D., Xiao, X., de Casteele, M. V., Mellitzer, G., Ling, Z., Pipeleers, D., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.015 · Cited by 1,010
In vitro cultivation of human islets from expanded ductal tissue
Bonner‐Weir, S., Taneja, M., Weir, G. C., Tatarkiewicz, K., Song, K., Sharma, A., & O’Neil, J. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.14.7999 · Cited by 978
Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841
Pancreas organogenesis: From bud to plexus to gland
Pan, F. C., & Wright, C. V. E. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22584 · Cited by 647
KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma
Morris, J. P., Wang, S. C., & Hebrok, M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2899 · Cited by 597
Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium
Kim, K., Kakitani, M., Zhao, J., Oshima, T., Tang, T., Binnerts, M. E., Liu, Y., Boyle, B., Park, E., Emtage, P. C. R., et al. (2005) · Science · doi:10.1126/science.1112521 · Cited by 587
SOX9 is required for maintenance of the pancreatic progenitor cell pool
Seymour, P. A., Freude, K., Tran, M. N., Mayes, E., Jensen, J. N., Kist, R., Scherer, G., & Sander, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609217104 · Cited by 567
Self-citationSeaberg, R. M., Smukler, S. R., Kieffer, T. J., Enikolopov, G., Shyr, Z. A., Wheeler, M. B., Korbutt, G. S., & van der Kooy, D. (2004) · Nature Biotechnology · doi:10.1038/nbt1004 · Cited by 562
Growth and Regeneration of Adult β Cells Does Not Involve Specialized Progenitors
Teta, M., Rankin, M. M., Long, S. Y., Stein, G. M., & Kushner, J. A. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.04.011 · Cited by 551
A Multipotent Progenitor Domain Guides Pancreatic Organogenesis
Zhou, Q., Law, A. C., Rajagopal, J., Anderson, W. J., Gray, P. A., & Melton, D. A. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.06.001 · Cited by 550
The Vascular Basement Membrane: A Niche for Insulin Gene Expression and β Cell Proliferation
Nikolova, G. V., Jabs, N., Konstantinova, I., Domogatskaya, A., Tryggvason, K., Sorokin, L. M., Fässler, R., Gu, G., Gerber, H., Ferrara, N., et al. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.01.015 · Cited by 514
Solar, M., Cardalda, C. A., Houbracken, I., Martı́n, M., Maestro, M. A., Medts, N. D., Xu, X., Grau, V., Heimberg, H., Bouwens, L., et al. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.11.003 · Cited by 503
Kopp, J. L., Dubois, C. L., Schaffer, A. E., Hao, E., Shih, H.-P., Seymour, P. A., Ma, J., & Sander, M. (2011) · Development · doi:10.1242/dev.056499 · Cited by 486
Self-citationInada, A., Nienaber, C. E., Katsuta, H., Fujitani, Y., Levine, J., Morita, R., Sharma, A., & Bonner‐Weir, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805803105 · Cited by 453
Johansson, K., Dursun, U., Jordan, N., Gu, G., Beermann, F., Gradwohl, G., & Grapin‐Botton, A. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.02.010 · Cited by 337
Rovira, M., Scott, S.-G., Liss, A. S., Jensen, J. N., Thayer, S. P., & Leach, S. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912589107 · Cited by 296
Nam, J., Turcotte, T. J., Smith, P. F., Choi, S., & Yoon, J. K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508324200 · Cited by 288
Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells
Narsinh, K. H., Sun, N., Sánchez-Freire, V., Lee, A. S., de Almeida, P. E., Hu, S., Jan, T. A., Wilson, K. D., Leong, D. E., Rosenberg, J., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44635 · Cited by 287
Schaffer, A. E., Freude, K., Nelson, S. B., & Sander, M. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.05.015 · Cited by 278
Self-citationMinami, K., Okuno, M., Miyawaki, K., Okumachi, A., Ishizaki, K., Oyama, K., Kawaguchi, M., Ishizuka, N., Iwanaga, T., & Seino, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507567102 · Cited by 261
Gao, R., Ustinov, J., Pulkkinen, M., Lundin, K., Korsgren, O., & Otonkoski, T. (2003) · Diabetes · doi:10.2337/diabetes.52.8.2007 · Cited by 246
Otonkoski, T., Beattie, G. M., Mally, M. I., Ricordi, C., & Hayek, A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116723 · Cited by 244
The Adult Mouse and Human Pancreas Contain Rare Multipotent Stem Cells that Express Insulin
Smukler, S. R., Arntfield, M. E., Razavi, R., Bikopoulos, G. J., Karpowicz, P. A., Seaberg, R. M., Dai, F. F., Lee, S., Ahrens, R., Fraser, P. E., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.01.015 · Cited by 230
Stabilization of β-catenin impacts pancreas growth
Heiser, P. W., Lau, J., Taketo, M. M., Herrera, P. L., & Hebrok, M. (2006) · Development · doi:10.1242/dev.02366 · Cited by 227
Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas
Immervoll, H., Hoem, D., Sakariassen, P. Ø., Steffensen, O. J., & Molven, A. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-48 · Cited by 206
Liu, J. C., Heilshorn, S. C., & Tirrell, D. A. (2004) · Biomacromolecules · doi:10.1021/bm034340z · Cited by 188
Self-citationPancreatic neurogenin 3-expressing cells are unipotent islet precursors
Desgraz, R., & Herrera, P. L. (2009) · Development · doi:10.1242/dev.039214 · Cited by 170
Heller, R. S., Dichmann, D. S., Jensen, J. N., Miller, C., Wong, G. G., Madsen, O. D., & Serup, P. (2002) · Developmental Dynamics · doi:10.1002/dvdy.10157 · Cited by 167
Wang, S., Yan, J., Anderson, D. A., Xu, Y., Kanal, M. C., Cao, Z., Wright, C. V. E., & Gu, G. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.12.009 · Cited by 155
杉山, 拓., Rodriguez, R. T., McLean, G. W., & Kim, S. K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609490104 · Cited by 155
Differentiation of Affinity-Purified Human Pancreatic Duct Cells to β-Cells
Yatoh, S., Dodge, R., Akashi, T., Omer, A., Sharma, A., Weir, G. C., & Bonner‐Weir, S. (2007) · Diabetes · doi:10.2337/db06-1670 · Cited by 142
Oshima, Y., Suzuki, A., Kawashimo, K., Ishikawa, M., Ohkohchi, N., & Taniguchi, H. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.11.027 · Cited by 137
Githens, S. (1988) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-198807000-00004 · Cited by 126
Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a
Miyatsuka, T., Kosaka, Y., Kim, H., & German, M. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004842108 · Cited by 120
Kopinke, D., & Murtaugh, L. C. (2010) · BMC Developmental Biology · doi:10.1186/1471-213x-10-38 · Cited by 116
Schreiber, F. S., Deramaudt, T. B., Brunner, T. B., Boretti, M. I., Gooch, K. J., Stoffers, D. A., Bernhard, E. J., & Rustgi, A. K. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.03.058 · Cited by 104
Movassat, J., Beattie, G. M., Lopez, A. D., & Hayek, A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020137 · Cited by 103
Hanley, K. P., Ball, S. G., Keeling, J. W., Mansoor, S., Wilson, D. I., & Hanley, N. A. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00145-4 · Cited by 98
Staal, F. J. T., & Luis, T. C. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22467 · Cited by 93
Stem Cell Marker Prominin-1/AC133 Is Expressed in Duct Cells of the Adult Human Pancreas
Lardon, J., Corbeil, D., Huttner, W. Β., Ling, Z., & Bouwens, L. (2008) · Pancreas · doi:10.1097/mpa.0b013e318149f2dc · Cited by 90
Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis
Cortijo, C., Gouzi, M., Tissir, F., & Grapin‐Botton, A. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.016 · Cited by 89
In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells
Gao, R., Ustinov, J., Korsgren, O., & Otonkoski, T. (2005) · Diabetologia · doi:10.1007/s00125-005-1935-8 · Cited by 84
Blaine, S. A., Ray, K. C., Anunobi, R., GANNON, M. A., Washington, M. K., & Means, A. L. (2010) · Development · doi:10.1242/dev.048421 · Cited by 77
Pancreatitis and Calcium Signalling
Sutton, R., Petersen, O. H., & Pandol, S. J. (2008) · Pancreas · doi:10.1097/mpa.0b013e3181675010 · Cited by 56
Pancreatic Ductal Morphogenesis and the Pdx1 Homeodomain Transcription Factor
Wescott, M. P., Rovira, M., Reichert, M., von Burstin, J., Means, A. L., Leach, S. D., & Rustgi, A. K. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-03-0203 · Cited by 50
Evaluation of Pancreatic Cancer With Raman Spectroscopy in a Mouse Model
Pandya, A. K., Serhatkulu, G. K., Cao, A., Kast, R. E., Dai, H., Rabah, R. M., Poulik, J. M., Banerjee, S., Naik, R., Adsay, V. N., et al. (2008) · Pancreas · doi:10.1097/mpa.0b013e31815a3f1c · Cited by 41
Hori, Y., Fukumoto, M., & Kuroda, Y. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0192 · Cited by 38
Kilic, G., Wang, J., & Sosa‐Pineda, B. (2006) · Developmental Dynamics · doi:10.1002/dvdy.20729 · Cited by 33
Insulin-Expressing Colonies Developed From Murine Embryonic Stem Cell–Derived Progenitors
Ku, H. T., Chai, J., Kim, Y. J., White, P., Purohit-Ghelani, S., Kaestner, K. H., & Bromberg, J. S. (2007) · Diabetes · doi:10.2337/db06-0468 · Cited by 28
Self-citationPancreatic Progenitor Cells—Recent Studies
Ku, H. T. (2008) · Endocrinology · doi:10.1210/en.2008-0546 · Cited by 25
Self-citationChen, C., Chai, J., Singh, L., Kuo, C.-Y., Jin, L., Feng, T., Marzano, S., Galeni, S., Zhang, N., Iacovino, M., et al. (2011) · Assay and drug development technologies · doi:10.1089/adt.2010.0314 · Cited by 20
Self-citationA Quantitative Assay for Insulin-expressing Colony-forming Progenitors
Winkler, M., Trieu, N., Tao, F., Jin, L., Walker, S., Singh, L., & Ku, H. T. (2011) · Journal of Visualized Experiments · doi:10.3791/3148 · Cited by 11
Self-citationPancreatic cells and their progenitors.
Salpeter, S., & Dor, Y. (2006) · Methods in Enzymology · doi:10.1016/s0076-6879(06)19013-8 · Cited by 5
A Quantitative Assay for Insulin-expressing Colony-forming Progenitors
Winkler, M., Trieu, N., Feng, T., Jin, L., Walker, S., Singh, L., & Ku, H. T. (2011) · Journal of Visualized Experiments · doi:10.3791/3148-v · Cited by 3
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Huch, M., Bonfanti, P., Boj, S. F., Sato, T., Loomans, C. J. M., van de Wetering, M., Sojoodi, M., Li, V. S. W., Schuijers, J., Gracanin, A., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.204 · Cited by 726
3D biofabrication strategies for tissue engineering and regenerative medicine
Bajaj, P., Schweller, R. M., Khademhosseini, A., West, J. L., & Bashir, R. (2014) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105155 · Cited by 632
Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture
Li, X., Nadauld, L. D., Ootani, A., Corney, D. C., Pai, R. K., Gevaert, O., Cantrell, M. A., Rack, P. G., Neal, J. T., Chan, C. W. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3585 · Cited by 449
Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409
Self-citationPancreas Organogenesis: From Lineage Determination to Morphogenesis
Shih, H.-P., Wang, A., & Sander, M. (2013) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122405 · Cited by 347
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Metadata
- Authors
- Jin, L., Feng, T., Shih, H. P., Zerda, R., Luo, A., Hsu, J., Mahdavi, A., Sander, M., Tirrell, D. A., Riggs, A. D., & Ku, H. T.
- Affiliations
- Department of Diabetes and Metabolic Diseases Research,
- University of California San Diego (US)
- Electron Microscopy Core, and
- Department of Bioengineering, and
- California Institute of Technology (US)
- City Of Hope National Medical Center (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-19
- Volume
- 110
- Issue
- 10
- Pages
- 3907-3912
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3593860
- OpenAlex
- W2160112404
- Cited by
- 108
- References
- 60
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 6
- FWCI
- 14.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- National Cancer Institute (P30CA-33572, P30CA033572)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK078803, R01DK081587, R01DK078803, U01DK089533)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- pancreatic progenitor cells, Matrigel, beta-like cells, insulin secretion, self-renewal, pancreatic development, semi-solid culture
- MeSH terms
- Animals, Cell Differentiation, Collagen, Colony-Forming Units Assay, Culture Media, Drug Combinations, Islets of Langerhans, Laminin, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Pancreas, Proteoglycans, Hydrogels, Microscopy, Electron, Transmission, Insulin-Secreting Cells, Mice, Basic Helix-Loop-Helix Proteins, Wnt Signaling Pathway, Acinar Cells
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