The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Embryonic endocrine pancreas and mature β cells acquire α and PP cell phenotypes upon Arx misexpression
Open accessAbstract
Aristaless-related homeobox (Arx) was recently demonstrated to be involved in pancreatic alpha cell fate specification while simultaneously repressing the beta and delta cell lineages. To establish whether Arx is not only necessary, but also sufficient to instruct the alpha cell fate in endocrine progenitors, we used a gain-of-function approach to generate mice conditionally misexpressing this factor. Mice with forced Arx expression in the embryonic pancreas or in developing islet cells developed a dramatic hyperglycemia and eventually died. Further analysis demonstrated a drastic loss of beta and delta cells. Concurrently, a remarkable increase in the number of cells displaying alpha cell or, strikingly, pancreatic polypeptide (PP) cell features was observed. Notably, the ectopic expression of Arx induced in embryonic or adult beta cells led to a loss of the beta cell phenotype and a concomitant increase in a number of cells with alpha or PP cell characteristics. Combining quantitative real-time PCR and lineage-tracing experiments, we demonstrate that, in adult mice, the misexpression of Arx, rather than its overexpression, promotes a conversion of beta cells into glucagon- or PP-producing cells in vivo. These results provide important insights into the complex mechanisms underlying proper pancreatic endocrine cell allocation and cell identity acquisition.
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Cites
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Cited by
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Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
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Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure
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Developmental biology of the pancreas: A comprehensive review
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Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis
Ben-Othman, N., Vieira, A., Courtney, M., Record, F., Gjernes, E., Avolio, F., Hadzic, B., Druelle, N., Napolitano, T., Navarro-Sanz, S., et al. (2017) · Cell · doi:10.1016/j.cell.2016.11.002 · Cited by 322
Self-citation
Metadata
- Authors
- Collombat, P., Hecksher-Sørensen, J., Krull, J., Berger, J., Riedel, D., Herrera, P. L., Serup, P., & Mansouri, A.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-04-02
- Volume
- 117
- Issue
- 4
- Pages
- 961-970
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2103391067
- Cited by
- 256
- References
- 37
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Collombat, P., Hecksher-Sørensen, J., Krull, J., Berger, J., Riedel, D., Herrera, P. L., Serup, P., & Mansouri, A. (2007). Embryonic endocrine pancreas and mature β cells acquire α and PP cell phenotypes upon Arx misexpression. Journal of Clinical Investigation. https://doi.org/10.1172/jci29115
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