Single-Cell Lineage Analysis Reveals Extensive Multimodal Transcriptional Control during Directed Beta-Cell Differentiation

Investigators generated 95,308 single-cell transcriptomes and reconstructed a lineage tree of the entire differentiation process from human embryonic stem cells to beta-like cells to study temporally regulated genes during differentiation.
[Nature Metabolism]
Weng, C., Xi, J., Li, H., Cui, J., Gu, A., Lai, S., Leskov, K., Ke, L., Jin, F., & Li, Y. (2020). Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation. Nature Metabolism, 1–16. https://doi.org/10.1038/s42255-020-00314-2 Cite
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A Novel lncRNA PTTG3P/miR-132/212–3p/FoxM1 Feedback Loop Facilitates Tumorigenesis and Metastasis of Pancreatic Cancer

The authors found that pseudogene pituitary tumor-transforming 3 (PTTG3P) was significantly upregulated in PDAC tissues. Elevated PTTG3P expression correlated with larger tumor size and worse differentiation, and reduced overall survival.
[Cell Death Discovery]
Liu, W., Tang, J., Zhang, H., Kong, F., Zhu, H., Li, P., Li, Z., Kong, X., & Wang, K. (2020). A novel lncRNA PTTG3P/miR-132/212-3p/FoxM1 feedback loop facilitates tumorigenesis and metastasis of pancreatic cancer. Cell Death Discovery, 6(1), 1–15. https://doi.org/10.1038/s41420-020-00360-5 Cite
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Aberrant (Pro)renin Receptor Expression Induces Genomic Instability in Pancreatic Ductal Adenocarcinoma through Upregulation of SMARCA5/SNF2H

Scientists showed whether aberrant expression of (Pro)renin receptor [(P)RR] directly led to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells showed obvious cellular atypia.
[Communications Biology]
Shibayama, Y., Takahashi, K., Yamaguchi, H., Yasuda, J., Yamazaki, D., Rahman, A., Fujimori, T., Fujisawa, Y., Takai, S., Furukawa, T., Nakagawa, T., Ohsaki, H., Kobara, H., Wong, J. H., Masaki, T., Yuzawa, Y., Kiyomoto, H., Yachida, S., Fujimoto, A., & Nishiyama, A. (2020). Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H. Communications Biology, 3(1), 1–14. https://doi.org/10.1038/s42003-020-01434-x Cite
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The Many Lives of Myc in the Pancreatic β-Cell

The authors summarize the previous and recent knowledge of Myc in the β-cell, its potential for β-cell regeneration and its physiological importance for neonatal and adaptive β-cell expansion.
[Journal of Biological Chemistry]
Rosselot, C., Baumel-Alterzon, S., Li, Y., Brill, G., Lambertini, L., Katz, L. S., Lu, G., García-Ocaña, A., & Scott, D. K. (2020). The Many Lives of Myc in the Pancreatic β-Cell. Journal of Biological Chemistry, jbc.REV120.011149. https://doi.org/10.1074/jbc.REV120.011149 Cite
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Mesenchymal Stem Cells Promote Pancreatic β-Cell Regeneration through Downregulation of FoxO1 Pathway

Researchers evaluated the regenerative potential of the murine pancreas post-human telomerase reverse transcriptase mesenchymal stem cells (hTERT-MSC) administration through the intrapancreatic and intravenous route. Both routes of hTERT-MSC transplantation increased the incorporation of BrdU by pancreatic β-cells compared to control.
[Current Stem Cell Research & Therapy]
Khatri, R., Mazurek, S., Petry, S. F., & Linn, T. (2020). Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway. Stem Cell Research & Therapy, 11(1), 497. https://doi.org/10.1186/s13287-020-02007-9 Cite
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Government of Canada and JDRF Canada Announce New Research Funding to Accelerate Stem Cell-Based Therapies for Type 1 Diabetes

To mark the end of Diabetes Awareness Month, Sonia Sidhu, Member of Parliament for Brampton South, on behalf of the Honourable Patty Hajdu, Minister of Health, announced an investment of $6 million through the CIHR-JDRF Partnership to Defeat Diabetes for two Canadian research teams to accelerate the development of stem cell-based therapies for the treatment of type 1 diabetes.
[Juvenile Diabetes Research Foundation]
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Dr. Stanley Riddell awarded Burke O’Reilly Family Endowed Chair in Immunotherapy

Riddell’s lab is working to make CAR T-cell therapies even better and expand the repertoire of cancers it can treat. Based out of the Hutch’s new Steam Plant facility, he and his colleagues are zeroing in on multiple myeloma as the next likely new target for the approach.
[Fred Hutchinson Cancer Research Center]
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Concerted Cell and In Vivo Screen for Pancreatic Ductal Adenocarcinoma (PDA) Chemotherapeutics

Cultured primary PDA cells expressed Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo.
[Scientific Reports]
Layeghi-Ghalehsoukhteh, S., Pal Choudhuri, S., Ocal, O., Zolghadri, Y., Pashkov, V., Niederstrasser, H., Posner, B. A., Kantheti, H. S., Azevedo-Pouly, A. C., Huang, H., Girard, L., MacDonald, R. J., Brekken, R. A., & Wilkie, T. M. (2020). Concerted cell and in vivo screen for pancreatic ductal adenocarcinoma (PDA) chemotherapeutics. Scientific Reports, 10(1), 20662. https://doi.org/10.1038/s41598-020-77373-8 Cite
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Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia

Researchers showed that activation of mTORC1 signaling was sufficient to induce chronic hyperglucagonemia as a result of α-cell proliferation, cell size and mass expansion. Hyperglucagonemia in a conditional deletion of the mTORC1 inhibitor, TSC2, in α-cells was associated with an increase in glucagon content and enhanced glucagon secretion.
[Diabetes]
Kramer, N. B., Lubaczeuski, C., Blandino-Rosano, M., Barker, G., Gittes, G. K., Caicedo, A., & Bernal-Mizrachi, E. (2020). Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia. Diabetes. https://doi.org/10.2337/db20-0440 Cite
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Dual Self-Regulated Delivery of Insulin and Glucagon by a Hybrid Patch

The authors describe a transdermal patch that mimics the inherent counterregulatory effects of β-cells and α-cells for blood glucose management by dynamically releasing insulin or glucagon.
[Proceedings of the National Academy of Sciences of the United States of America]
Wang, Z., Wang, J., Li, H., Yu, J., Chen, G., Kahkoska, A. R., Wu, V., Zeng, Y., Wen, D., Miedema, J. R., Buse, J. B., & Gu, Z. (2020). Dual self-regulated delivery of insulin and glucagon by a hybrid patch. Proceedings of the National Academy of Sciences, 117(47), 29512–29517. https://doi.org/10.1073/pnas.2011099117 Cite
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Wisp1 Is a Circulating Factor That Stimulates Proliferation of Adult Mouse and Human Beta Cells

Scientists report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. They showed that Wisp1 promoted endogenous and transplanted adult beta cell proliferation in vivo.
[Nature Communications]
Fernandez-Ruiz, R., García-Alamán, A., Esteban, Y., Mir-Coll, J., Serra-Navarro, B., Fontcuberta-PiSunyer, M., Broca, C., Armanet, M., Wojtusciszyn, A., Kram, V., Young, M. F., Vidal, J., Gomis, R., & Gasa, R. (2020). Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells. Nature Communications, 11(1), 5982. https://doi.org/10.1038/s41467-020-19657-1 Cite
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