KRT7 Marks an Airway Glandular Ductal Stem Cell Population That Supports Multilineage Development and Regeneration
- 1The University of Alabama at Birmingham
Abstract
Airway submucosal glands (SMGs) play a central role in host defense through mucus secretion, airway hydration, and mucociliary clearance. However, the hierarchical organization of glandular progenitor populations remains poorly defined, largely because SMGs are sparse and restricted to the proximal trachea in murine models. Using the ferret, a model that closely recapitulates the gland-rich submucosal architecture of human cartilaginous airways, we identify KRT7+ glandular ductal epithelial cells as a progenitor population. In both adult ferret and healthy human airways, KRT7 expression is primarily restricted to the SMG duct epithelium, where it is co-expressed with KRT19 and CD166 but only partially overlaps with ALDH1A1. During early postnatal development, KRT7 expression becomes progressively restricted to glandular ductal epithelium and is ultimately excluded from mature acinar, myoepithelial cells, and KRT5+/KRT14+ basal lineages. Fate mapping in KRT7CreER;ROSAmTmG transgenic ferrets revealed that KRT7-lineage cells serve as multipotent progenitors during SMG morphogenesis, generating both serous and mucous epithelial cells. Following severe airway injury, KRT7-lineage cells survive within gland ducts and rapidly expand to repair the damaged surface epithelium by differentiating into ciliated and secretory cells but not KRT5+ basal cells. In organoid cultures, glandular KRT7-lineage cells acquired a KRT5+ basal-like phenotype and generated multilineage epithelia with functional CFTR-mediated transport. These findings identify the KRT7+ ductal niche as a critical progenitor reservoir for airway development, homeostasis, and regeneration, with implications for cystic fibrosis therapies.
Related
- A synthetic xeno-free extracellular matrix surrogate supports robust human induced pluripotent stem cell maintenance and multilineage differentiation
- Shared molecular and cellular programs during regeneration of glandular epithelia
- Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection
- A regenerative fibroblast competence field supports multiple cell fates in adult skin regeneration
- OsVIPP1 Supports Rice Leaf Chloroplast Development and Is Associated with Seed Metabolic Changes and Yield-Related Traits
BibTeX
@misc{hu2026krt7,
title = {{KRT7 Marks an Airway Glandular Ductal Stem Cell Population That Supports Multilineage Development and Regeneration}},
author = {Z. Hu and C. Wang and Y. Ma and Y. Yi and L. Yang and L. Jiang and Z. Yan and X. Sun and X. Liu and J. F. Engelhardt},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759678},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759678v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - KRT7 Marks an Airway Glandular Ductal Stem Cell Population That Supports Multilineage Development and Regeneration
AU - Z. Hu
AU - C. Wang
AU - Y. Ma
AU - Y. Yi
AU - L. Yang
AU - L. Jiang
AU - Z. Yan
AU - X. Sun
AU - X. Liu
AU - J. F. Engelhardt
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759678
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759678v1
AB - Airway submucosal glands (SMGs) play a central role in host defense through mucus secretion, airway hydration, and mucociliary clearance. However, the hierarchical organization of glandular progenitor populations remains poorly defined, largely because SMGs are sparse and restricted to the proximal trachea in murine models. Using the ferret, a model that closely recapitulates the gland-rich submucosal architecture of human cartilaginous airways, we identify KRT7+ glandular ductal epithelial cells as a progenitor population. In both adult ferret and healthy human airways, KRT7 expression is primarily restricted to the SMG duct epithelium, where it is co-expressed with KRT19 and CD166 but only partially overlaps with ALDH1A1. During early postnatal development, KRT7 expression becomes progressively restricted to glandular ductal epithelium and is ultimately excluded from mature acinar, myoepithelial cells, and KRT5+/KRT14+ basal lineages. Fate mapping in KRT7CreER;ROSAmTmG transgenic ferrets revealed that KRT7-lineage cells serve as multipotent progenitors during SMG morphogenesis, generating both serous and mucous epithelial cells. Following severe airway injury, KRT7-lineage cells survive within gland ducts and rapidly expand to repair the damaged surface epithelium by differentiating into ciliated and secretory cells but not KRT5+ basal cells. In organoid cultures, glandular KRT7-lineage cells acquired a KRT5+ basal-like phenotype and generated multilineage epithelia with functional CFTR-mediated transport. These findings identify the KRT7+ ductal niche as a critical progenitor reservoir for airway development, homeostasis, and regeneration, with implications for cystic fibrosis therapies.
ER -