Mouse pancreatic islet scRNA-seq atlas across sexes, ages, and stress conditions including diabetes

To better understand pancreatic β-cell heterogeneity we generated a mouse pancreatic islet atlas capturing a wide range of biological conditions. The atlas contains scRNA-seq datasets of over 300,000 mouse pancreatic islet cells, of which more than 100,000 are β-cells, from nine datasets with 56 samples, including two previously unpublished datasets. The samples vary in sex, age (ranging from embryonic to aged), chemical stress, and disease status (including T1D NOD model development and two T2D models, mSTZ and db/db) together with different diabetes treatments.

We used the atlas to obtain new insights into islet biology that could not have been obtained from individual datasets. This includes holistic description of the β-cell landscape across datasets and conditions, identification of similarities and differences between diabetes models, and disentanglement of molecular pathways involved in different types of β-cell dysfunction.

Figure 1: The mouse islet atlas (MIA) of scRNA-seq datasets across conditions offers new insights into islet and β-cell biology. Highlighted are (a) MIA content, including different conditions: sex, age, diabetes models (STZ, db/db, NOD) and anti-diabetic treatments, and chemical stress (application of different chemicals such as FoxO inhibitor), (b) putative novel biological insights, (c) analyses enabled by MIA that would not have been possible on individual datasets, and (d) potential use cases of MIA as a resource for future studies.

Citation:

Hrovatin K, Bastidas-Ponce A, Bakhti M, Zappia L, Buttner M, Sallino C, Sterr M, Bottcher A, Migliorini A, Lickert H*, Theis FJ*. bioRxiv, 2022. Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas

* Corresponding authors

Resources:

• Interactive exploartion of the atlas in the cellxgene browser or computational access via Sfaira: https://cellxgene.cziscience.com/collections/296237e2-393d-4e31-b590-b03f74ac5070
• scArches model for mapping new data onto the atlas: https:/theislab/mm_pancreas_atlas_rep/tree/main/reference_mapping/data/scArches, for use instructions see the reference_mapping directory.
• Integrated atlas and newly generated datasets on GEO: GSE211799.

Reproducbility code:

• Paper reproducibility: reproducibility directory.
• Instructions for reference mapping: reference_mapping directory.