biostudies-literatureNimkulrat SDNIDDK NIH HHSNCRR NIH HHS2058-2066https://www.ebi.ac.uk/biostudies/studies/S-EPMC8576426biostudies-literatureUnknown70(9)Loss of mature β-cell function and identity, or β-cell dedifferentiation, is seen in both type 1 and type 2 diabetes. Two competing models explain β-cell dedifferentiation in diabetes. In the first model, β-cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β-cells resemble β-cell progenitors. In the second model, β-cell dedifferentiation depends on the type of diabetogenic stress. This model, which we call the "Anna Karenina" model, predicts that in each type of diabetes, β-cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β-cell-specific lineage-tracing system coupled with RNA sequencing in mice. We cDiabetesThe Anna Karenina Model of β-Cell Maturation in Development and Their Dedifferentiation in Type 1 and Type 2 Diabetes.PMC8576426S10 RR025483R56 DK115837Nimkulrat SDNi ZBernstein MNBrown JKendziorski CBlum BfalseThe Anna Karenina Model of β-Cell Maturation in Development and Their Dedifferentiation in Type 1 and Type 2 Diabetes.Loss of mature β-cell function and identity, or β-cell dedifferentiation, is seen in both type 1 and type 2 diabetes. Two competing models explain β-cell dedifferentiation in diabetes. In the first model, β-cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β-cells resemble β-cell progenitors. In the second model, β-cell dedifferentiation depends on the type of diabetogenic stress. This model, which we call the "Anna Karenina" model, predicts that in each type of diabetes, β-cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β-cell-specific lineage-tracing system coupled with RNA sequencing in mice. We c2021-01-01T00:00:00Z2021 Sep2025-04-18T18:43:02.071Z2025-04-07T06:24:26.405ZS-EPMC85764263441726410.2337/db21-0211