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.
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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]
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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.
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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
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]
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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]
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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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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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.
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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
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.
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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]
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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
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.
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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