دورية أكاديمية
Use of Induced Pluripotent Stem Cells to Build Isogenic Systems and Investigate Type 1 Diabetes.
| العنوان: | Use of Induced Pluripotent Stem Cells to Build Isogenic Systems and Investigate Type 1 Diabetes. |
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| المؤلفون: | Armitage LH; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Stimpson SE; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Santostefano KE; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; Center for Cellular Reprogramming, College of Medicine, University of Florida, Gainesville, FL, United States.; Century Therapeutics, iPSC Biology, Philadelphia, PA, United States., Sui L; Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY, United States., Ogundare S; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Newby BN; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Castro-Gutierrez R; Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, United States., Huber MK; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Taylor JP; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States., Sharma P; Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States., Radichev IA; Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States., Perry DJ; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Fredette NC; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; Center for Cellular Reprogramming, College of Medicine, University of Florida, Gainesville, FL, United States., Savinov AY; Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States., Wallet MA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States.; Century Therapeutics, Immunology, Philadelphia, PA, United States., Terada N; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; Center for Cellular Reprogramming, College of Medicine, University of Florida, Gainesville, FL, United States., Brusko TM; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Russ HA; Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, United States., Chen J; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States., Egli D; Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Columbia University, New York, NY, United States., Mathews CE; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.; University of Florida Diabetes Institute, University of Florida, Gainesville, FL, United States.; Center for Cellular Reprogramming, College of Medicine, University of Florida, Gainesville, FL, United States. |
| المصدر: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2021 Nov 09; Vol. 12, pp. 737276. Date of Electronic Publication: 2021 Nov 09 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes/*pathology , Diabetes Mellitus, Type 1/*pathology , Induced Pluripotent Stem Cells/*pathology, Cell Differentiation/physiology ; Humans ; Insulin-Secreting Cells/pathology ; Islets of Langerhans/pathology |
| مستخلص: | Type 1 diabetes (T1D) is a disease that arises due to complex immunogenetic mechanisms. Key cell-cell interactions involved in the pathogenesis of T1D are activation of autoreactive T cells by dendritic cells (DC), migration of T cells across endothelial cells (EC) lining capillary walls into the islets of Langerhans, interaction of T cells with macrophages in the islets, and killing of β-cells by autoreactive CD8 + T cells. Overall, pathogenic cell-cell interactions are likely regulated by the individual's collection of genetic T1D-risk variants. To accurately model the role of genetics, it is essential to build systems to interrogate single candidate genes in isolation during the interactions of cells that are essential for disease development. However, obtaining single-donor matched cells relevant to T1D is a challenge. Sourcing these genetic variants from human induced pluripotent stem cells (iPSC) avoids this limitation. Herein, we have differentiated iPSC from one donor into DC, macrophages, EC, and β-cells. Additionally, we also engineered T cell avatars from the same donor to provide an in vitro platform to study genetic influences on these critical cellular interactions. This proof of concept demonstrates the ability to derive an isogenic system from a single donor to study these relevant cell-cell interactions. Our system constitutes an interdisciplinary approach with a controlled environment that provides a proof-of-concept for future studies to determine the role of disease alleles (e.g. IFIH1, PTPN22, SH2B3, TYK2) in regulating cell-cell interactions and cell-specific contributions to the pathogenesis of T1D. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Armitage, Stimpson, Santostefano, Sui, Ogundare, Newby, Castro-Gutierrez, Huber, Taylor, Sharma, Radichev, Perry, Fredette, Savinov, Wallet, Terada, Brusko, Russ, Chen, Egli and Mathews.) |
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| معلومات مُعتمدة: | R01 DK125360 United States DK NIDDK NIH HHS; R01 DK103585 United States DK NIDDK NIH HHS; P01 AI042288 United States AI NIAID NIH HHS; UC4 DK104207 United States DK NIDDK NIH HHS; T32 DK108736 United States DK NIDDK NIH HHS; U24 DK098085 United States DK NIDDK NIH HHS; P30 DK116073 United States DK NIDDK NIH HHS; UH3 DK122638 United States DK NIDDK NIH HHS; R01 DK120444 United States DK NIDDK NIH HHS; R21 AI140044 United States AI NIAID NIH HHS; F30 DK105788 United States DK NIDDK NIH HHS; R24 GM119977 United States GM NIGMS NIH HHS; T32 GM136444 United States GM NIGMS NIH HHS; R01 DK127497 United States DK NIDDK NIH HHS; UL1 TR001427 United States TR NCATS NIH HHS; UC4 DK104194 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: autoimmunity; beta cells; human; immunity; induced pluripotent stem cells; isogenic; type 1 diabetes mellitus |
| تواريخ الأحداث: | Date Created: 20211203 Date Completed: 20220215 Latest Revision: 20230617 |
| رمز التحديث: | 20230620 |
| مُعرف محوري في PubMed: | PMC8630743 |
| DOI: | 10.3389/fendo.2021.737276 |
| PMID: | 34858326 |
| قاعدة البيانات: | MEDLINE |
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