Collections / Spatial transcriptomics reveals microenvironmental heterogeneity in osteoarthritic subchondral bone

Spatial transcriptomics reveals microenvironmental heterogeneity in osteoarthritic subchondral bone

Although increasing evidence implicates subchondral bone alterations in osteoarthritis, the spatial organization of subchondral bone remodeling remains unclear. Applying spatial transcriptomics on human subchondral bone, we identify a spatially conserved osteogenic core-halo architecture that displays transcriptional reprogramming in sclerotic microenvironments. Spatial dependency and a customized cell-cell communication framework reveal disrupted osteoblast-osteoclast spatial coupling, enhanced osteoblast-mesenchymal interactions, and identify FN1-SDC2 and COL1A1-DDR2 as candidate stromal-osteogenic signaling axes that may contribute to aberrant bone remodeling. Additionally, we present the first in situ transcriptional landscape of osteocytes and reveal its potential regulatory role in aberrant bone remodeling. We further delineate a continuum of spatial ecotypes exhibiting distinct enrichment, spatial topology reorganization, and inter-ecotype communication rewiring across pathological states. Metabolic flux inference additionally reveals substrate-limited, stressed states across multiple ecotypes in sclerotic microenvironments. Collectively, our findings provide critical insights into aberrant subchondral bone remodeling in osteoarthritis and offer a valuable framework for future mechanistic studies and therapeutic exploration.

Datasets4
Size~179 MB
AssayVisium
Samplehuman · multiple
KindOther
www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE342703 ↗
Python · lamindb
import lamindb as ln
import spatialdata as sd

coll = ln.Collection.get(key="geo-gse342703")
coll.ordered_artifacts.df()                 # the 4 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()}
Open in Vitessce
Visium
Human pancreas
GSM9936743
human pancreas pancreatic ductal adenocarcinoma 37 MB 14,400 obs silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuepancreas
Conditionpancreatic ductal adenocarcinoma
Size37 MB
Obs14,400
silver H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human head of femur
GSM9936744
human head of femur osteoarthritis 45 MB 14,400 obs silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuehead of femur
Conditionosteoarthritis
Size45 MB
Obs14,400
silver H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human head of femur
GSM9936742
human head of femur osteoarthritis 48 MB 14,400 obs silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuehead of femur
Conditionosteoarthritis
Size48 MB
Obs14,400
silver H&E NCBI GEO policy Open in Vitessce
Open in Vitessce
Visium
Human head of femur
GSM9936741
human head of femur osteoarthritis 49 MB 14,400 obs silver H&E NCBI GEO policy
TechnologyVisium
Organismhuman
Tissuehead of femur
Conditionosteoarthritis
Size49 MB
Obs14,400
silver H&E NCBI GEO policy Open in Vitessce

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