A spatial transcriptomic atlas of acute neonatal lung injury across development and disease severity

Jonathan A. Kropski, Jennifer M. S. Sucre, Nicholas E. Banovich
, *Corresponding author
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Description A molecular understanding of lung organogenesis requires delineation of the timing and drivers of spatial-temporal cellular movements that ultimately form and support a surface capable of gas exchange. While the advent of single-cell transcriptomics has allowed for the discovery and identification of transcriptionally distinct populations present during lung development, the spatiotemporal dynamics of these transcriptional shifts remain undefined. With imaging-based spatial transcriptomics, we analyzed the gene expression patterns in 17 human infant lungs at varying stages of development and lung injury, creating a spatial transcriptomics atlas of ~1.2 million cells. We applied computational clustering approaches to identify shared molecular similarities among this cohort, establishing a framework that will generate hypotheses about how tissue architecture and molecular spatial relationships are coordinated during normal development and disrupted in disease. Recognizing that all preterm birth represents an injury to the developing lung, we have moved away from the conventional paradigm of classifying an infants as “disease” or “control” in favor of a linear regression approach that accounted for the routinely collected object measures of gestational age, life span, and disease severity. Within this new framework, we have identified cell type patterns across these variables that would likely be overlooked when using a binary conventional “diseased vs. control” comparison. Together, these data represent a resource for the lung research community, supporting discovery-based inquiry and identification of targetable molecular mechanisms in both normal and arrested human lung development. We profiled 17 infant lung samples that were collected from the Human Infant Lung Repository at Vanderbilt University with a gene probeset of 343 genes using the 10X Genomics Xenium platform. Sample names were generated by appending ‘PDL’ and then ranged from ‘001’ - ‘017’ (ex. PDL001). This dataset is comprised of individuals that range from the canalicular stage of lung development to the alveolar, with variable levels of disease pathologies. We took a 3x3 μ square of each tissue and arranged them in a tissue micro-array. We then took two adjacent serial sections and ran them concurrently, generating two technical replicates per sample.
Dataset ID LMEX0000090001
Assay Type Xenium
Organism Human
Technology 10x Genomics Xenium
Reference Banovich et al. (2025)
External databases GEO: GSE297945
SampleDonorAgeHealth StatusSample TypeTobaccoCell CountGEO Sample
PDL001_slide1PDL00116 weeksFetalNot viable25664GSM9002269
PDL001_slide2PDL00116 weeksFetalNot viable27103GSM9002286
PDL002_slide1PDL00218 weeksFetalNot viable133974GSM9002270
PDL002_slide2PDL00218 weeksFetalNot viable71523GSM9002287
PDL003_slide1PDL00321 weeksPreterm - uninjuredPrematurity153933GSM9002271
PDL003_slide2PDL00321 weeksPreterm - uninjuredPrematurity154419GSM9002288
PDL004_slide1PDL00430 weeksPreterm - injuredNecrotizing enterocolitis39027GSM9002272
PDL004_slide2PDL00430 weeksPreterm - injuredNecrotizing enterocolitis37903GSM9002289
PDL005_slide2PDL00524 weeksPreterm - uninjuredPrematurity33955GSM9002291
PDL007_slide1PDL00728 weeksPreterm - injuredPulmonary Hypoplasia64221GSM9002275
PDL007_slide2PDL00728 weeksPreterm - injuredPulmonary Hypoplasia60831GSM9002292
PDL008_slide1PDL00843 weeksPreterm - injuredBPD23359GSM9002276
PDL008_slide2PDL00843 weeksPreterm - injuredBPD25704GSM9002293
PDL010_slide1PDL01038 weeksTerm - uninjuredMeningitis60874GSM9002279
PDL010_slide2PDL01038 weeksTerm - uninjuredMeningitis54457GSM9002296
PDL011_slide1PDL01135 ish weeksTerm - uninjuredHypoxic-Ischemic Encephalopathy69475GSM9002280
PDL011_slide2PDL01135 ish weeksTerm - uninjuredHypoxic-Ischemic Encephalopathy52821GSM9002297
PDL012_slide1PDL01240 weeksTerm - uninjuredHypoxic-Ischemic Encephalopathy19074GSM9002283
PDL012_slide2PDL01240 weeksTerm - uninjuredHypoxic-Ischemic Encephalopathy14730GSM9002300
PDL013_slide1PDL01336 weeksTerm - uninjuredEncephalitis67711GSM9002284
PDL013_slide2PDL01336 weeksTerm - uninjuredEncephalitis67642GSM9002301
PDL014_slide1PDL01429 weeksRare disease (CHAOS)CHAOS syndrome53036GSM9002278
PDL014_slide2PDL01429 weeksRare disease (CHAOS)CHAOS syndrome73381GSM9002295
PDL016_slide1PDL01663 weeksRare disease (Infant BPD)ARB fetopathy (severe BPD)45275GSM9002281
PDL016_slide2PDL01663 weeksRare disease (Infant BPD)ARB fetopathy (severe BPD)38508GSM9002298
PDL017_slide2PDL017NARare disease (Adult BPD)BPD (explant of adult with BPD)8972GSM9002302
LungMAP IDAlt IDSpeciesHealth Status
LMSP0000090001PDL001_slide1Homo sapiensFetal
LMSP0000090013PDL001_slide2Homo sapiensFetal
LMSP0000090002PDL002_slide1Homo sapiensFetal
LMSP0000090014PDL002_slide2Homo sapiensFetal
LMSP0000090003PDL003_slide1Homo sapiensPreterm - uninjured
LMSP0000090015PDL003_slide2Homo sapiensPreterm - uninjured
LMSP0000090004PDL004_slide1Homo sapiensPreterm - injured
LMSP0000090016PDL004_slide2Homo sapiensPreterm - injured
LMSP0000090017PDL005_slide2Homo sapiensPreterm - uninjured
LMSP0000090005PDL007_slide1Homo sapiensPreterm - injured
LMSP0000090018PDL007_slide2Homo sapiensPreterm - injured
LMSP0000090006PDL008_slide1Homo sapiensPreterm - injured
LMSP0000090019PDL008_slide2Homo sapiensPreterm - injured
LMSP0000090007PDL010_slide1Homo sapiensTerm - uninjured
LMSP0000090020PDL010_slide2Homo sapiensTerm - uninjured
LMSP0000090008PDL011_slide1Homo sapiensTerm - uninjured
LMSP0000090021PDL011_slide2Homo sapiensTerm - uninjured
LMSP0000090009PDL012_slide1Homo sapiensTerm - uninjured
LMSP0000090022PDL012_slide2Homo sapiensTerm - uninjured
LMSP0000090010PDL013_slide1Homo sapiensTerm - uninjured
LMSP0000090023PDL013_slide2Homo sapiensTerm - uninjured
LMSP0000090011PDL014_slide1Homo sapiensRare disease (CHAOS)
LMSP0000090024PDL014_slide2Homo sapiensRare disease (CHAOS)
LMSP0000090012PDL016_slide1Homo sapiensRare disease (Infant BPD)
LMSP0000090025PDL016_slide2Homo sapiensRare disease (Infant BPD)
LMSP0000090026PDL017_slide2Homo sapiensRare disease (Adult BPD)