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Generation of Stem Cell-Derived β Cells from Type 1 Diabetic Patients

ABSTRACT: We recently reported the scalable in vitro production of functional stem cell-derived β cells. Here we extend this approach to generate SC-β cells from Type 1 diabetic patients (T1D), a cell type that is destroyed during disease progression and has not been possible to extensively study. These cells express β cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice, and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β cell stress. Using these assays, we find no major differences in T1D SC-β cells compared to SC-β cells derived from non-diabetic patients (ND). These results show that T1D SC-β cells can be used for the treatment of diabetes, drug screening, and the study of β cell biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70901 | GEO | 2016/04/01

SECONDARY ACCESSION(S): PRJNA289894

REPOSITORIES: GEO

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Generation of Stem Cell-Derived Î² Cells from Type 1 Diabetic Patients

Project description:We recently reported the scalable in vitro production of functional stem cell-derived Î² cells. Here we extend this approach to generate SC-Î² cells from Type 1 diabetic patients (T1D), a cell type that is destroyed during disease progression and has not been possible to extensively study. These cells express Î² cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice, and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of Î² cell stress. Using these assays, we find no major differences in T1D SC-Î² cells compared to SC-Î² cells derived from non-diabetic patients (ND). These results show that T1D SC-Î² cells can be used for the treatment of diabetes, drug screening, and the study of Î² cell biology. Differentiated cells were sorted and processed for RNA isolation using the MARIS protocol published previously (PMID: 24516164.) Human induced pluripotent stem cell (hiPSC) line were differentiated into SC-beta cells or dysfunctional, polyhormonal cells (PH). Four biological replicates were assessed with differentiation to both SC-beta and PH cells. Those data were normalized together with and compared to existing, previously published data from Hrvatin et al. (PMID: 24516164) and Pagliuca et al. (PMID: 25303535) from human islet-derived insulin+ cells, undifferentiated HUES8 hES cells, SC-beta cells derived from HUES8 and PH cells derived from HUES8 according to previously published protocols.

2016-04-01 | E-GEOD-70901 | biostudies-arrayexpress

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Project description:Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclosphosphamide. Human β cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long term survival of β cells in some patients.

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A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes

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2024-01-01 | GSE228219 | GEO

microRNAs of thymocytes and of peripheral and pancreas-infiltrating T lymphocytes

Project description:As early as one month of age, nonobese diabetic (NOD) mice feature pancreatic infiltration of autoreactive T lymphocytes, which destruct insulin-producing beta cells, producing autoimmune diabetes mellitus (T1D) within eightmonths. Thus, we hypothesized that during the development of T1D, the transcriptional modulation of immune reactivity genes may occur as thymocytes mature into peripheral T lymphocytes. The transcriptome of thymocytes and peripheral CD3+ T lymphocytes from prediabetic or diabetic mice analyzed through microarray hybridizations identified the differentially expressed genes.

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2022-11-10 | PXD025394 | Pride

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