Single cell profiling of human airway identifies tuft-ionocyte progenitor cells displaying cytokine-dependent differentiation bias in vitro

Single cell profiling of human airway identifies tuft-ionocyte progenitor cells displaying cytokine-dependent differentiation bias in vitro

Abstract Human airways contain specialized rare epithelial cells including CFTR-rich ionocytes that regulate airway surface physiology and chemosensory tuft cells that produce asthma-associated inflammatory mediators. Here, using a lung cell atlas of 311,748 single cell RNA-Seq profiles, we identify...

Full description

Saved in:
Bibliographic Details
Main Authors: Viral S. Shah, Avinash Waghray, Brian Lin, Atharva Bhagwat, Isha Monga, Michal Slyper, Bruno Giotti, Sunghyun Kim, Dawei Sun, Ke Xu, Eric Park, Mohamad Bairakdar, Jiajie Xu, Julia Waldman, Danielle Dionne, Lan T. Nguyen, Wendy Lou, Peiwen Cai, Christoph Muus, Jiawei Sun, Manalee V. Surve, Lujia Cha Cha Yang, Orit Rozenblatt-Rosen, Toni M. Delorey, Srinivas Vinod Saladi, Aviv Regev, Jayaraj Rajagopal, Alexander M. Tsankov
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60441-w
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Human airways contain specialized rare epithelial cells including CFTR-rich ionocytes that regulate airway surface physiology and chemosensory tuft cells that produce asthma-associated inflammatory mediators. Here, using a lung cell atlas of 311,748 single cell RNA-Seq profiles, we identify 687 ionocytes (0.45%). In contrast to prior reports claiming a lack of ionocytes in the small airways, we demonstrate that ionocytes are present in small and large airways in similar proportions. Surprisingly, we find only 3 mature tuft cells (0.002%), and demonstrate that previously annotated tuft-like cells are instead highly replicative progenitor cells. These tuft-ionocyte progenitor (TIP) cells produce ionocytes as a default lineage. However, Type 2 and Type 17 cytokines divert TIP cell lineage in vitro, resulting in the production of mature tuft cells at the expense of ionocyte differentiation. Our dataset thus provides an updated understanding of airway rare cell composition, and further suggests that clinically relevant cytokines may skew the composition of disease-relevant rare cells.
ISSN:2041-1723

Similar Items