The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression
Open accessAbstract
BACKGROUND: Insulin producing beta cell and glucagon producing alpha cells are colocalized in pancreatic islets in an arrangement that facilitates the coordinated release of the two principal hormones that regulate glucose homeostasis and prevent both hypoglycemia and diabetes. However, this intricate organization has also complicated the determination of the cellular source(s) of the expression of genes that are detected in the islet. This reflects a significant gap in our understanding of mouse islet physiology, which reduces the effectiveness by which mice model human islet disease. RESULTS: To overcome this challenge, we generated a bitransgenic reporter mouse that faithfully labels all beta and alpha cells in mouse islets to enable FACS-based purification and the generation of comprehensive transcriptomes of both populations. This facilitates systematic comparison across thousands of genes between the two major endocrine cell types of the islets of Langerhans whose principal hormones are of cardinal importance for glucose homeostasis. Our data leveraged against similar data for human beta cells reveal a core common beta cell transcriptome of 9900+ genes. Against the backdrop of overall similar beta cell transcriptomes, we describe marked differences in the repertoire of receptors and long non-coding RNAs between mouse and human beta cells. CONCLUSIONS: The comprehensive mouse alpha and beta cell transcriptomes complemented by the comparison of the global (dis)similarities between mouse and human beta cells represent invaluable resources to boost the accuracy by which rodent models offer guidance in finding cures for human diabetes.
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The Na-K ATPase of both mouse and human β-cells is predominantly composed of α1-, β1- and β3-subunits.
“A tetrameric complex of two α- and two β-subunits, the Na-K ATPase of both mouse and human β-cells is predominantly composed of α1-, β1- and β3-subunits (56, 68).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [56]
The Results section on functional validation discusses ATP-sensitive potassium channels, but not the Na-K ATPase or its subunit composition. Searches for Na-K ATPase, sodium-potassium pump, and the α1/β1/β3 subunit gene names found no passage establishing the claimed composition in mouse and human β-cells. (LLM, conf=0.72)
Experimental — accuracy not yet measuredRyrs are only expressed at low levels in mouse β-cells.
“However, Ryrs are only expressed at low levels in mouse β-cells (56).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [56]
The Results sections on mouse β-cell gene expression discuss other receptors and ion channels, but do not state the expression level of Ryrs. Searches for Ryr, Ryr1–3, and ryanodine receptors found no passage addressing the claim in our copy. (LLM, conf=0.70)
Experimental — accuracy not yet measuredMouse β-cells express Slc1a5 (ASCT20), which mediates Na+-dependent uptake of glutamate.
“Mouse β-cells express Slc1a5 (encoding the transporter ASCT20) (56), which mediates Na+-dependent uptake of glutamate into the β-cell (Appendix Figure 11A).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [56]
The citation is attached to the statement that mouse β-cells express Slc1a5, encoding ASCT20; the uptake claim is instead linked to an appendix figure. The Results section on functional validation names other β-cell transporters, but searches of our copy for Slc1a5 and ASCT20 found no passage addressing their expression in mouse β-cells. (LLM, conf=0.72)
Experimental — accuracy not yet measuredMouse β-cells express Epac2 at approximately 10-fold higher levels than their human counterparts.
“Interestingly, mouse β-cells express Epac2 at ≈10-fold higher levels than their human counterparts (56).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [56]
The Results section, under “Comprehensive comparison of mouse and human beta cell transcriptomes” (page unavailable), reports genes with more than 10-fold higher expression in mouse β-cells, but does not identify Epac2 among them. Searches for Epac2 and Rapgef4 found no passage stating its mouse-to-human expression ratio. (LLM, conf=0.72)
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SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cellsPreprint
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- Authors
- Benner, C., van der Meulen, T., Cacéres, E., Tigyi, K., Donaldson, C. J., & Huising, M. O.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Huising, Mark O
- Venue
- BMC Genomics
- Published
- 2014-07-22
- Volume
- 15
- Issue
- 1
- Pages
- 620-620
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC4124169
- OpenAlex
- W2139458690
- Cited by
- 302
- References
- 76
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 11 · 2023: 44 · 2022: 24 · 2021: 30 · 2020: 33 · 2019: 20 · 2018: 27 · 2017: 41 · 2016: 24 · 2015: 18 · 2014: 1
- FWCI
- 27.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Vanderbilt University
- National Institutes of Health (DK026741)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK026741)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- pancreatic beta cells, alpha cells, islet transcriptome, long non-coding RNA, species differences, human-mouse comparison, receptor repertoire, diabetes model, glucose homeostasis, insulin, glucagon
- MeSH terms
- Red Fluorescent Protein, Animals, Flow Cytometry, Glucagon, Humans, Luminescent Proteins, Receptors, Cell Surface, RNA, Transcription Factors, Gene Library, Sequence Analysis, RNA, Glucagon-Secreting Cells, Insulin-Secreting Cells, Mice, Transcriptome, RNA, Long Noncoding
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