Modular design of synthetic receptors for programmed gene regulation in cell therapies

Zhu I, Liu R, Garcia JM, Hyrenius-Wittsten A, Piraner DI, Alavi J, Israni DV, Liu B, Khalil AS, Roybal KT.
Cell. 2022 Apr 14;185(8):1431-1443.e16. doi: 10.1016/j.cell.2022.03.023. PMID:35427499

Of Interest Diabetes Study of Children of Diverse Ethnicity and Race: Study design Golden age of immunoengineering Regulatory approval of islet transplantation for treatment of type 1 diabetes: Implications and what is on the horizon Stem cell-derived islet therapy: is this the end of the beginning? Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas A structural blueprint for interleukin-21 signal modulation Screening and prevention of type 1 diabetes: Where are we? Loss of ZNF148 enhances insulin secretion in human pancreatic β cells Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes Longitudinal MRI Shows Progressive Decline in Pancreas Size and Altered Pancreas Shape in Type 1 Diabetes Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways Identifying type 2 diabetes risk genes by β-cell CRISPR screening Targeted delivery of harmine to xenografted human pancreatic islets promotes robust cell proliferation Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells Hypothesis: Induction of Autoimmunity in Type 1 Diabetes-A Lipid Focus Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes IL18 signaling causes islet β cell development and insulin secretion via different receptors on acinar and β cells Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation Deep Visual Proteomics defines single-cell identity and heterogeneity Modular design of synthetic receptors for programmed gene regulation in cell therapies Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells Genetic manipulation of stress pathways can protect stem-cell-derived islets from apoptosis in vitro Abnormal exocrine-endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8 New insights into β-cell failure, regeneration and replacement Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation Using the T Cell Receptor as a Biomarker in Type 1 Diabetes Pancreatic islets in bed with microvasculature-companions for life Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium α-cell Gq signaling is critical for maintaining euglycemia A human ESC line for efficient CRISPR editing of pluripotent stem cells The physiological role of β-cell heterogeneity in pancreatic islet function Mutations and variants of ONECUT1 in diabetes Loss of TBX3 enhances pancreatic progenitor generation from human pluripotent stem cells Chromogranin A Deficiency Confers Protection from Autoimmune Diabetes Via Multiple Mechanisms Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes SARS-CoV-2 infection of islet β cells: Evidence and implications Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection Engineering islets from stem cells for advanced therapies of diabetes Generation of insulin-producing pancreatic β cells from multiple human stem cell lines Defining a cure for type 1 diabetes: a call to action
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