Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation

Liyue Li, Linyi Jiao, Danni Feng, Yizhang Yuan, Xiaoqian Yang, Jian Li, Dong Jiang, Hexin Chen, Qingxiang Meng, Ruchong Chen, Bixing Fang, Xuenong Zou, Zhenhua Luo, Xiaoyan Ye, Yue Hong, Chun Liu () and Chunwei Li ()
Additional contact information
Liyue Li: The First Affiliated Hospital, Sun Yat-sen University
Linyi Jiao: The First Affiliated Hospital, Sun Yat-sen University
Danni Feng: The First Affiliated Hospital, Sun Yat-sen University
Yizhang Yuan: The First Affiliated Hospital, Sun Yat-sen University
Xiaoqian Yang: The First Affiliated Hospital of Sun Yat-sen University
Jian Li: The First Affiliated Hospital, Sun Yat-sen University
Dong Jiang: The First Affiliated Hospital of Sun Yat-sen University
Hexin Chen: The First Affiliated Hospital, Sun Yat-sen University
Qingxiang Meng: Guangzhou First People’s Hospital
Ruchong Chen: Guangzhou Medical University
Bixing Fang: The First Affiliated Hospital, Sun Yat-sen University
Xuenong Zou: The First Affiliated Hospital of Sun Yat-sen University
Zhenhua Luo: The First Affiliated Hospital of Sun Yat-sen University
Xiaoyan Ye: The First Affiliated Hospital, Sun Yat-sen University
Yue Hong: Hainan University
Chun Liu: The First Affiliated Hospital of Sun Yat-sen University
Chunwei Li: The First Affiliated Hospital, Sun Yat-sen University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44488-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44488-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44488-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().