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The Anna Karenina model of β cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes

ABSTRACT: The Anna Karenina model of β cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes

PROVIDER: PRJNA713802 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13939100.fastq.gz	Fastqsanger.gz
	SRR13939101.fastq.gz	Fastqsanger.gz
	SRR13939102.fastq.gz	Fastqsanger.gz
	SRR13939103.fastq.gz	Fastqsanger.gz
	SRR13939104.fastq.gz	Fastqsanger.gz

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The Anna Karenina model of β cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes

Project description:Loss of mature β cell function and identity, or β cell dedifferentiation, is seen in all types of diabetes mellitus. 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 constructed a multidimensional map of β cell transcriptional trajectories during the normal course of β cell postnatal development, and during their dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-Lepob/ob). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated β cells, β cells dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between different types of diabetes.

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