Single-cell spatial transcriptomics of an inducible destabilized-domain Cre mouse line to target disease associated microglia

This dataset contains the results from a single-cell spatial
transcriptomics experiment performed using Bruker Nanostring CosMx
technology on 10µm thick fresh-frozen coronal brain sections from the
following groups: 5xFAD hemizygous, Cst7 DD-Cre, Ai14tdTomato
double heterozygous (AD, n = 3), and Cst7 DD-Cre/Ai14tdTomato
double heterozygous (WT, n = 1) mice treated with TMP, and Cst7
DD-Cre/Ai14tdTomato double heterozygous mice treated with cuprizone (CPZ)
and TMP (CPZ, n = 2). The dataset is provided as an .RDS file,
which includes raw and corrected counts, along with comprehensive
metadata. Metadata includes experimental group, sample ID, cell type
annotations, and X-Y coordinates of each cell. The function of microglia
during progression of Alzheimer's disease (AD) can be investigated
using mouse models that enable genetic manipulation of microglial
subpopulations in a temporal manner. We developed mouse lines that express
either Cre recombinase (Cre) for constitutive targeting, or
destabilized-domain Cre recombinase (DD-Cre) for inducible targeting from
the Cst7 locus (Cst7 DD-Cre) to specifically manipulate disease associated
microglia (DAM) and crossed with Ai14 tdTomato cre-reporter line mice.
Cst7Cre was found to target all brain resident myeloid cells, due to
transient developmental expression of Cst7, but no expression was found in
the inducible Cst7 DD-Cre mice. Further crossing of this line with 5xFAD
mice combined with dietary administration of trimethoprim to induce DD-Cre
activity produces long-term labeling in DAM without evidence of leakiness,
with tdTomato-expression restricted to cells surrounding plaques. Using
this model, we found that DAMs are a subset of plaque-associated microglia
(PAMs) and their transition to DAM increases with age and disease stage.
Spatial transcriptomic analysis revealed that tdTomato+ cells show higher
expression of disease and inflammatory genes compared to other microglial
populations, including non-labeled PAMs. These models allow either
complete cre-loxP targeting of all brain myeloid cells (Cst7Cre), or
inducible targeting of DAMs, without leakiness (Cst7 DD-Cre).