A mouse model for monitoring islet cell genesis and developing therapies for diabetes

Shimajiri, Yoshinori; Kosaka, Yasuhiro; Scheel, David; Lynn, Francis C.; Kishimoto, Nina Y.; Wang, Juehu; ShuHong, Zhao; German, Michael S.

doi:10.1242/dmm.002998

Cited by 11 publications

(10 citation statements)

References 45 publications

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“…Kras LSL-G12D mice (Jackson et al, 2001) and C57BL/6(tetO-Cdkn1b)1Scpr/J mice (Pruitt et al, 2013) were purchased from Jackson Laboratory. Sox9-rtTA transgenic mice were made by recombining the reverse tetracycline transactivator (Clontech; pTet-On) into the Sox9 coding region of a 202kb BAC (RP23-36D5); transgenic mice were generated by the UCSF transgenic core as described (Shimajiri et al, 2011). Transgene expression was induced in pregnant Sox9-rtTA; tetO-Cdkn1b with daily 1 mg intraperitoneal (IP) injections of doxycycline on indicated gestational days.…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors

Krentz

Hoof

et al. 2017

Developmental Cell

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SUMMARY During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint. Using models of mouse and human pancreas development, we show that lengthening of the G1 phase of the pancreatic progenitor cell cycle is essential for proper induction of NEUROG3 and initiation of endocrine cell differentiation. In sum, these studies demonstrate that progenitor cell-cycle G1 lengthening, through its actions on stabilization of NEUROG3, is an essential variable in normal endocrine cell genesis.

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Section: Methodsmentioning

confidence: 99%

Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors

Krentz

Hoof

et al. 2017

Developmental Cell

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“…In 50 women vaccinated with HPV16/18 AS04-adjuvanted vaccine, serum SEAP levels correlated with antibody levels measured using ELISA (Kemp et al, 2008). In addition to the measurement of SEAP in blood, it is a useful reporter for in situ histo-enzymatic revelation to correlate the level of its secretion and the number of transduced cells (Shimajiri et al, 2011). …”

Section: Secreted Alkaline Phosphatasementioning

confidence: 99%

Secreted blood reporters: Insights and applications

Tannous¹,

Teng²

2011

Biotechnology Advances

188

206

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Secreted reporters which are detected in the blood/serum/urine have shown to be simple and useful tools for ex vivo real-time monitoring of in vivo biological processes. Here we explore the three most commonly used secreted blood reporters in experimental animals: secreted alkaline phosphatase, soluble peptides derived from human carcinoembryonic antigen and human chorionic gonadotropin, and Gaussia luciferase. We also comment on other recently discovered secreted reporters and their potential use as blood reporters for multiplexing applications.

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“…GDF11 is a key factor in embryonic development, metabolic disorders, and cancers (33,43). Previous studies have shown that restoring systemic GDF11 level reversed age-related cardiac hypertrophy and brain dysfunction (20,23).…”

Section: Introductionmentioning

confidence: 99%

Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation

Wang

et al. 2018

American Journal of Physiology-Gastrointestinal and Liver Physi

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Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The NLRP3 (Nod-like receptor family pyrin domain-1 containing 3) inflammasome is closely associated with intestinal inflammation due to its ability to increase IL-1β secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sulfate sodium (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index (DAI), shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1β secretion and NLRP3 inflammasome activation in colon samples and RAW264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the TLR4/NF-κB p65 pathway and reactive oxygen species (ROS) production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC.

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A mouse model for monitoring islet cell genesis and developing therapies for diabetes

Cited by 11 publications

References 45 publications

Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors

Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors

Secreted blood reporters: Insights and applications

Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation

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