Collections / Pericyte KATP Channel Hyperactivity Redistributes Cortical Blood Flow in a CADASIL Mouse Model

Pericyte KATP Channel Hyperactivity Redistributes Cortical Blood Flow in a CADASIL Mouse Model

Spatial transcriptomics on WT versus CADASIL mouse model with brain and isolated vasculature

Datasets8
Size~3.3 GB
AssaysVisium HD · Visium
Samplemouse · multiple
KindComparison
Flag a data issue
10.1038/s44161-026-00844-0 ↗
Python · sddb client
from sddb import Catalog

cohort = Catalog().collection("geo-gse335702")
cohort.members        # the 8 datasets as a table

print(cohort.licenses())              # check the terms before you download

sdatas = cohort.to_dict()             # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")
Python · lamindb

Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.

import lamindb as ln

db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse335702")
coll.ordered_artifacts.to_dataframe()   # the 8 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
Shell
# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse335702 --dest data/

Licenses: 4 NCBI GEO policy, 4 CC BY 4.0

Pericyte K<sub>ATP</sub> channel hyperactivity redistributes cortical blood flow in a CADASIL mouse model.

Cerebral hemodynamic dysfunction is a key driver of unhealthy brain aging. Impaired microcirculatory reactivity leads to uneven perfusion, rendering deeper brain regions more vulnerable and thereby contributing to cognitive decline. Yet how capillaries contribute to these deficits remains poorly defined. Here we combined spatial transcriptomics with in vivo two-photon and three-photon imaging to measure layer-specific cerebral blood flow in control and small vessel disease model mice (CADASIL TgNotch3R169C). We found downregulation of ATP-synthesizing genes, indicating microvascular metabolic impairment that paralleled impaired pericyte bioenergetics. This energy deficit coincided with diminished tone in the arteriole-capillary transitional zone and reduced deep-layer perfusion. Complementary electrophysiology, ex vivo and in silico approaches, revealed that hyperactive K<sub>ATP</sub> channels in pericytes drive a redistribution of cerebral blood flow toward superficial cortical layers. This loss of spatial perfusion equalization, despite preserved global flow, contributed to deep-layer hypoperfusion, establishing a previously underrecognized but tractable vascular function disrupted in aging pathology.

Open in Vitessce
Visium HD
Mouse brain
GSM9817885
mouse brain 705 MB 384,475 bins bronze H&E NCBI GEO policy
TechnologyVisium HD
Organismmouse
Tissuebrain
Size705 MB
Bins384,475
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817886
mouse brain 674 MB 217,363 bins bronze H&E NCBI GEO policy
TechnologyVisium HD
Organismmouse
Tissuebrain
Size674 MB
Bins217,363
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817887
mouse brain cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 1.1 GB 346,469 bins bronze H&E NCBI GEO policy
TechnologyVisium HD
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size1.1 GB
Bins346,469
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817888
mouse brain cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 700 MB 267,238 bins bronze H&E NCBI GEO policy
TechnologyVisium HD
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size700 MB
Bins267,238
bronze H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Mouse brain
GSM9817881
mouse brain 43.1 MB H&E
TechnologyVisium
Organismmouse
Tissuebrain
Size43.1 MB
H&E Open in Vitessce
Open in Vitessce
Visium
Mouse brain
GSM9817882
mouse brain cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 29.7 MB 2,077 spots silver H&E
TechnologyVisium
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size29.7 MB
Spots2,077
silver H&E Open in Vitessce
Open in Vitessce
Visium
Mouse cerebral blood vessel
GSM9817883
mouse cerebral blood vessel 25.0 MB 831 spots silver H&E
TechnologyVisium
Organismmouse
Tissuecerebral blood vessel
Size25.0 MB
Spots831
silver H&E Open in Vitessce
Open in Vitessce
Visium
Mouse cerebral blood vessel
GSM9817884
mouse cerebral blood vessel cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 26.4 MB 632 spots silver H&E
TechnologyVisium
Organismmouse
Tissuecerebral blood vessel
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size26.4 MB
Spots632
silver H&E Open in Vitessce

Cite this collection

doi.org/10.1038/s44161-026-00844-0 ↗
BibTeX
@article{Jeffrey_2026,
  title = {Pericyte KATP channel hyperactivity redistributes cortical blood flow in a CADASIL mouse model},
  volume = {5},
  ISSN = {2731-0590},
  url = {http://dx.doi.org/10.1038/s44161-026-00844-0},
  DOI = {10.1038/s44161-026-00844-0},
  number = {8},
  journal = {Nature Cardiovascular Research},
  publisher = {Springer Science and Business Media LLC},
  author = {Jeffrey, Danielle A. and Prince, Eric W. and Khakpour, Niloufar and Ferris, Hannah R. and Peters, Colin H. and Seedorf, Gregory and Romero, Phinea Z. and Bueno Guerrero, Mayra and Russell, Abigail N. and Glodoski, Katherine and Futia, Gregory L. and Bonney, Stephanie K. and Thornton, Michael A. and Gibson, Emily A. and Proenza, Catherine and Garcia, Anastacia M. and Tsoukias, Nikolaos M. and Dabertrand, Fabrice},
  year = {2026},
  month = Aug,
  pages = {725–743}
}