Carl, J. | Search bioRxiv

bioRxiv2026

A postnatal human lung developmental atlas reveals windows of genetic vulnerability to chronic lung disease

At birth, the lungs undergo an abrupt physiologic change, as the function of gas exchange transitions from the placenta to the lung. Subsequent postnatal development of the lungs is marked by a rapid and profound increase in the growth of the distal airways and alveolar gas exchange compartment. Insults during this period increase the risk of developing lung disease later in life, though how early-life events affect adult disease onset remains unclear. We generated a single-cell atlas of postnatal human lung development from birth through adulthood and mapped temporally regulated gene expression changes in each cell lineage. Using this atlas, we identified disease risk-associated genes with developmentally regulated expression. These analyses reveal cell type-specific and temporally restricted expression of genes associated with adult lung disease risk, including COPD. Heritability enrichment analysis demonstrated that COPD genetic risk is enriched in genes active during early postnatal endothelial development, linking early-life vascular maturation to adult disease susceptibility. These findings characterize the early window of susceptibility for adult chronic lung diseases and establish a framework to guide mechanistic studies of disease-associated genes.

developmental biology↗

bioRxiv2025

Single Nucleus Profiling Highlights the All-Brain Echinoderm Nervous System

Metazoans comprise diverse tissues and cell types, each essential for the survival of the organism. Most of these cell types are established early in embryogenesis and persist into adulthood. However, in indirectly developing sea urchins, the continuity between embryonic and adult stages is thus interrupted by a planktonic larval stage that undergoes complete metamorphosis. In addition, while the gene regulatory networks governing distinct embryonic and larval cell lineages are well studied, the molecular and morphological identities of post-metamorphic sea urchin cell types remain poorly understood. Here, we reconstructed the cell type atlas of post-metamorphic Paracentrotus lividus juveniles using single-nucleus transcriptomics, shedding light on the conservation of genetic regulatory mechanisms in post-metamorphic cell types. We identified cell signatures corresponding to eight distinct cell type groups and analyzed at least twenty-nine neuronal cell families, including fifteen unique photoreceptor cell signatures. By combining single cell transcriptomics with spatial gene expression analysis and high-resolution electron microscopy, we identified homologues of vertebrate neuronal genes and photoreceptive opsins expressed throughout the sea urchin body. These findings provide evidence that the echinoderm body plan is not only predominantly head-like, but also exhibits an all-brain organization in an animal previously considered to have a primitive nervous system.

evolutionary biology↗