Stevens, N. | Search bioRxiv

bioRxiv2026

Region-specific molecular regulatory programs define epithelial identity, progenitor states, and mucus homeostasis in human distal airways

Small distal airways differ from proximal large airways in structure, airflow dynamics, and epithelial composition, and represent a central site of muco-obstructive lung disease pathogenesis. However, due in part to their inaccessibility, the molecular mechanisms that establish regional epithelial identity and govern mucociliary defense in distal airway epithelia remain poorly defined. Here, we integrate transcriptomic, secretomic, and chromatin accessibility analyses of matched primary human large and small airway epithelial cultures to define region-specific regulatory networks. We identify distal airway-specific transcriptional and chromatin programs required for maintaining epithelial identity and mucus homeostasis. Loss of NKX2-1 impairs distal airway secretory cell (DASC) differentiation and shifts mucus properties toward a disease-associated state. Lineage-resolved organoid assays identify an NKX2-1-high distal airway basal cell population with hybrid basal-secretory features as a selective progenitor for DASCs. Collectively, these findings establish a molecular framework for distal airway epithelial biology and define mechanisms regulating region-specific mucociliary host defense.

Cell Biology↗

bioRxiv2021

Underwater dual-magnification imaging for automated lake plankton monitoring

We present an approach for automated in-situ monitoring of phytoplankton and zooplankton communities based on a dual magnification dark-field imaging microscope/camera. We describe the Dual Scripps Plankton Camera (DSPC) system and associated image processing, and assess its capabilities in detecting and characterizing plankton species of different size and taxonomic categories, and in measuring their abundances in both laboratory and field applications. In the laboratory, body size and abundance estimates by the DSPC significantly and robustly scale with the same measurements derived by traditional microscopy. In the field, a DSPC installed permanently at 3 m depth in Lake Greifensee (Switzerland), delivered images of plankton individuals, colonies, and heterospecific aggregates without disrupting natural arrangements of interacting organisms, their microenvironment or their behavior at hourly timescales. The DSPC was able to track the dynamics of taxa in the size range between [~]10 m to [~] 1 cm, covering virtually all the components of the planktonic food web (including parasites and potentially toxic cyanobacteria). Comparing data from the field-deployed DSPC to traditional sampling and microscopy revealed a general overall agreement in estimates of plankton diversity and abundances, despite imaging limitations in detecting small phytoplankton species and rare and large zooplankton taxa (e.g. carnivorous zooplankton). The most significant disagreements between traditional methods and the DSPC resided in the measurements of community properties of zooplankton, organisms that are heterogeneously distributed spatially and temporally, and whose demography appeared to be better captured by automated imaging. Time series collected by the DSPC depicted ecological succession patterns, algal bloom dynamics and circadian fluctuations with a temporal frequency and morphological resolution that would have been impossible with traditional methods. We conclude that the DSPC approach is suitable for stable long-term deployments, and robust for both research and water quality monitoring. Access to high frequency, reproducible and real-time data of a large spectrum of the planktonic ecosystem might represent a breakthrough in both applied and fundamental plankton ecology.

ecology↗