Browsing by Author "Melton, Douglas"

Now showing items 1-20 of 39

    • Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication 

      Annes, J. P.; Ryu, J. H.; Lam, K.; Carolan, Peter Joseph; Utz, K.; Hollister-Lock, J.; Anthony, Anthony; Rubin, Lee; Weir, Gordon Campbell; Melton, Douglas A. (Proceedings of the National Academy of Sciences, 2012)
      Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro- and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion ...

    • All β Cells Contribute Equally to Islet Growth and Maintenance 

      Brennand, Kristen; Huangfu, Danwei; Melton, Douglas (Public Library of Science, 2007)
      In healthy adult mice, the β cell population is not maintained by stem cells but instead by the replication of differentiated β cells. It is not known, however, whether all cells contribute equally to growth and maintenance, ...

    • Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation 

      Yi, Peng; Park, Ji Sun; Melton, Douglas A. (Elsevier BV, 2013)
      Replenishing insulin-producing pancreatic β cell mass will benefit both type I and type II diabetics. In adults, pancreatic β cells are generated primarily by self-duplication. We report on a mouse model of insulin resistance ...

    • Brief Report: VGLL4 Is a Novel Regulator of Survival in Human Embryonic Stem Cells 

      Tajonar, Adriana; Maehr, René; Hu, Guang; Sneddon, Julie Beth; Rivera-Feliciano, Jose; Cohen, Dena Elana; Elledge, Stephen J.; Melton, Douglas A. (AlphaMed Press, 2013)
      Human embryonic stem cells (hESCs) are maintained in a self-renewing state by an interconnected network of mechanisms that sustain pluripotency, promote proliferation and survival, and prevent differentiation. We sought ...

    • Charting Cellular Identity During Human in Vitro β-Cell Differentiation 

      Veres, Adrian; Faust, Aubrey; Bushnell, Henry; Engquist, Elise; Kenty, Jennifer; Harb, George; Poh, Yeh-Chuin; Sintov, Elad; Gürtler, Mads; Pagliuca, Felicia; Peterson, Quinn; Melton, Douglas (Springer Science and Business Media LLC, 2019-05)
      In vitro differentiation of human stem cells can produce pancreatic β-cells; the loss of this insulin-secreting cell type underlies type 1 diabetes. Here, as a step towards understanding this differentiation process, we ...

    • Exploring the Use of Human Pluripotent Stem Cells to Create Functional Pancreatic \(\beta\) Cells 

      Hrvatin, Sinisa (2013-03-18)
      Directed differentiation of human pluripotent stem cells (hPSCs) has the potential to produce human cell types that can be used for disease modeling and cell transplantation. Two key challenges in the differentiation from ...

    • Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3 

      Blum, Barak; Hrvatin, Sini[sbreve]?a; Schuetz, Christian; Bonal, Claire; Rezania, Alireza; Melton, Douglas A. (Nature Publishing Group, 2012)
      Insulin-expressing cells that have been differentiated from human pluripotent stem cells in vitro lack the glucose responsiveness characteristic of mature beta cells. Beta-cell maturation in mice was studied to find genetic ...

    • Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation 

      Chen, Alice E.; Borowiak, Malgorzata; Sherwood, Richard Irving; Kweudjeu, Anastasie; Melton, Douglas A. (The Company of Biologists, 2013)
      Embryonic stem (ES) cells hold great promise with respect to their potential to be differentiated into desired cell types. Of interest are organs derived from the definitive endoderm, such as the pancreas and liver, and ...

    • Generation of pluripotent stem cells from patients with type 1 diabetes 

      Maehr, René; Chen, Shuibing; Snitow, Melinda; Ludwig, Thomas; Yagasaki, Lisa; Goland, Robin; Leibel, Rudolph L.; Melton, Douglas A. (Proceedings of the National Academy of Sciences, 2009)
      Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would ...

    • Generation of stem cell-derived β-cells from patients with type 1 diabetes 

      Millman, Jeffrey R.; Xie, Chunhui; Van Dervort, Alana; Gürtler, Mads; Pagliuca, Felicia W.; Melton, Douglas A. (Nature Publishing Group, 2016)
      We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are ...

    • Genetic Approaches to Study Human Embryonic Stem Cell Self-Renewal and Survival 

      Tajonar, Adriana (2012-08-23)
      Embryonic stem (ES) cells can be maintained indefinitely in culture while retaining the ability to give rise to cellular derivatives from the three germ layers. These unique characteristics hold great promise for regenerative ...

    • Genetic Targeting of the Endoderm with Claudin-6CreER 

      Anderson, William J.; Zhou, Qiao; Alcalde, Victor; Kaneko, Osamu F; Blank, Leah J; Sherwood, Richard Irving; Guseh, James Sawalla; Rajagopal, Jayaraj; Melton, Douglas A. (Wiley-Blackwell, 2008)
      A full description of the ontogeny of the β cell would guide efforts to generate β cells from embryonic stem cells (ESCs). The first step requires an understanding of definitive endoderm: the genes and signals responsible ...

    • Genome-Scale in Vivo CRISPR Screen Identifies RNLS as a Target for Beta Cell Protection in Type 1 Diabetes 

      Cai, Erica P.; Ishikawa, Yuki; Zhang, Wei; de Carvalho Leite, Nayara; Li, Jian; Hou, Shurong; Kiaf, Badr; Hollister-Lock, Jennifer; Yilmaz, Nese Kurt; Schiffer, Celia A.; Melton, Douglas; Kissler, Stephan; Yi, Peng (Springer Science and Business Media LLC, 2020-07-27)
      Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Pluripotent stem cells can now be differentiated into beta cells, raising the prospect of a cell replacement therapy for T1D. However, ...

    • How to make a functional β-cell 

      Pagliuca, Felicia Jane; Melton, Douglas A. (The Company of Biologists, 2013)
      Insulin-secreting pancreatic β-cells are essential regulators of mammalian metabolism. The absence of functional β-cells leads to hyperglycemia and diabetes, making patients dependent on exogenously supplied insulin. Recent ...

    • How to make beta cells? 

      Borowiak, Malgorzata; Melton, Douglas A. (Elsevier, 2009)
      Insulin-producing beta cells are lost or insufficient in diabetic patients, presenting the medical challenge for new beta cells. Currently, there are three strategies that offer promise. One involves the generation of beta ...

    • Impracticality of Egg Donor Recruitment in the Absence of Compensation 

      Egli, Dieter; Chen, Alice E.; Saphier, Genevieve; Powers, Douglas; Alper, Michael Myron; Katz, Karin; Berger, Brian Max; Goland, Robin; Leibel, Rudolph L.; Melton, Douglas A.; Eggan, Kevin Carl (Elsevier BV, 2011)
      Unfertilized oocytes of many mammalian species can reprogram somatic cells to a pluripotent state. Human oocytes might therefore be useful for producing patient-derived pluripotent stem cells. Because they would carry the ...

    • An improved ScoreCard to assess the differentiation potential of human pluripotent stem cells 

      Tsankov, Alexander M.; Akopian, Veronika; Pop, Ramona; Chetty, Sundari; Gifford, Casey A.; Daheron, Laurence; Melton, Douglas A.; Tsankova, Nadejda M.; Meissner, Alexander (2015)
      Research on human pluripotent stem cells has been hampered by the lack of a standardized, quantitative, scalable assay of pluripotency. We have previously described an assay called ScoreCard that used gene expression ...

    • In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes 

      Li, Weida; Nakanishi, Mio; Zumsteg, Adrian; Shear, Matthew; Wright, Christopher; Melton, Douglas A; Zhou, Qiao (eLife Sciences Publications, Ltd, 2014)
      Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major ...

    • Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice 

      Vegas, Arturo J.; Veiseh, Omid; Gürtler, Mads; Millman, Jeffrey R.; Pagliuca, Felicia W.; Bader, Andrew R.; Doloff, Joshua C.; Li, Jie; Chen, Michael; Olejnik, Karsten; Tam, Hok Hei; Jhunjhunwala, Siddharth; Langan, Erin; Aresta-Dasilva, Stephanie; Gandham, Srujan; McGarrigle, James; Bochenek, Matthew A.; Hollister-Lock, Jennifer; Oberholzer, Jose; Greiner, Dale L.; Weir, Gordon C.; Melton, Douglas A.; Langer, Robert; Anderson, Daniel G. (2016)
      The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in diabetic patients1. Pancreas transplantation and the infusion of cadaveric islets are currently ...

    • MARIS: Method for Analyzing RNA following Intracellular Sorting 

      Hrvatin, Siniša; Deng, Francis; O'Donnell, Charles W.; Gifford, David K.; Melton, Douglas A. (Public Library of Science, 2014)
      Transcriptional profiling is a key technique in the study of cell biology that is limited by the availability of reagents to uniquely identify specific cell types and isolate high quality RNA from them. We report a Method ...