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~3.1 GB
AssaysVisium HD · Visium
Samplemouse · multiple
KindComparison
10.1038/s44161-026-00844-0 ↗
Download the whole collection
Python · lamindb 
import lamindb as ln
import spatialdata as sd

coll = ln.Collection.get(key="geo-gse335702")
coll.ordered_artifacts.df()                 # the 8 members, ordered

# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]

# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}
About the study

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.

Member datasets · 8
Open in Vitessce
Visium HD
Mouse brain
GSM9817885
mouse brain 672 MB 384,475 obs bronze H&E
TechnologyVisium HD
Organismmouse
Tissuebrain
Size672 MB
Obs384,475
bronze H&E Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817886
mouse brain 643 MB 217,363 obs bronze H&E
TechnologyVisium HD
Organismmouse
Tissuebrain
Size643 MB
Obs217,363
bronze H&E Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817887
mouse brain cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 1.0 GB 346,469 obs bronze H&E
TechnologyVisium HD
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size1.0 GB
Obs346,469
bronze H&E Open in Vitessce
Open in Vitessce
Visium HD
Mouse brain
GSM9817888
mouse brain cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 667 MB 267,238 obs bronze H&E
TechnologyVisium HD
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size667 MB
Obs267,238
bronze H&E Open in Vitessce
Open in Vitessce
Visium
Mouse brain
GSM9817881
mouse brain 41 MB H&E
TechnologyVisium
Organismmouse
Tissuebrain
Size41 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 28 MB 2,077 obs silver H&E
TechnologyVisium
Organismmouse
Tissuebrain
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size28 MB
Obs2,077
silver H&E Open in Vitessce
Open in Vitessce
Visium
Mouse cerebral blood vessel
GSM9817883
mouse cerebral blood vessel 24 MB 831 obs silver H&E
TechnologyVisium
Organismmouse
Tissuecerebral blood vessel
Size24 MB
Obs831
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 25 MB 632 obs silver H&E
TechnologyVisium
Organismmouse
Tissuecerebral blood vessel
Conditioncerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Size25 MB
Obs632
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}
}