Pulmonary neuroendocrine cell-derived exosomes regulate iron homeostasis and oxidative stress in lung neurons.
Overview
15 affiliations
- Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL, USA
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
- Department of Microbiology, Immunology and Cancer Biology (MIC) and the Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA, USA
- Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research (CPDR), Golden Meditech Centre for NeuroRegeneration Science (GMCNS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Institute for Airway Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, IL, USA
- Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Center for Translational Stem Cell Biology and HKUMed Laboratory of Cellular Therapeutics, University of Hong Kong, Hong Kong 999077, China
- Department of Surgery, The University of Hong Kong Shenzhen Hospital, Shenzhen 518053, China
- Department of Critical Care Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Abstract
Nicotine, the principal addictive component of cigarettes, is linked to cognitive decline and neurodegenerative alterations, likely through oxidative stress and impaired iron regulation in neurons. Yet, underlying molecular pathways remain unclear. This study examined the role of pulmonary neuroendocrine cells (PNECs) in smoke-induced neural changes. Using human pluripotent stem cells, we generated induced PNECs (iPNECs) to overcome culture limitations and performed mechanistic analyses. We found that nicotine exposure stimulates iPNECs to secrete exosomes enriched with serotransferrin, an iron-binding glycoprotein. Neurons internalizing these exosomes displayed elevated levels of transferrin receptor 1 (TFR1), divalent metal transporter 1, and duodenal cytochrome b, associated with ferritin accumulation, oxidative stress, and adenosine triphosphate depletion. Inhibition of TFR1 alleviated these effects. Furthermore, nicotine-triggered exosomes increased α-synuclein expression in neurons in a manner consistent with stress- and vulnerability-associated
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- bioproject:PRJNA1219183, at NCBI BioProject; found in “Data, code, and materials availability:”
- geo:GSE103354, at NCBI GEO; found in “Data, code, and materials availability:”
- zenodo:7332090, at Zenodo; found in “Data, code, and materials availability:”
Data, code, and materials availability
Single-cell RNA sequencing data of iLung (batches 1 and 2) used for Fig. 2 (D to I) and fig. S4 (A, B, and D) have been deposited in the Sequence Read Archive (SRA) database (BioProject accession number: PRJNA1219183; link: https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 18 authors, 14 MeSH terms, 1 funder, 73 references.
Cite
This paper
Thakur, A., Zhang, K., Chen, J., Mei, S., Chen, J., Verdiell, A., Jacobs, E., Mulder, L., Whitford, A., Iyaswamy, A., Chen, Y.-W., Cliffe, A., Esser-Kahn, A., Chen, B., Lian, Q., Solway, J., Xing, S., & Chen, H. J. (2026). Pulmonary neuroendocrine cell-derived exosomes regulate iron homeostasis and oxidative stress in lung neurons. Science advances, 12(15), eady2696. https://
BibTeX
@article{thakur2026pulmo
author = {Thakur, Abhimanyu and Zhang, Kui and Chen, Jonathan and Mei, Shuya and Chen, Jace and Verdiell, Apolline and Jacobs, Emily and Mulder, Liza and Whitford, Abigail and Iyaswamy, Ashok and Chen, Ya-Wen and Cliffe, Anna and Esser-Kahn, Aaron and Chen, Bohao and Lian, Qizhou and Solway, Julian and Xing, Shunpeng and Chen, Huanhuan Joyce},
title = {{Pulmonary neuroendocrine cell-derived exosomes regulate iron homeostasis and oxidative stress in lung neurons}},
journal = {Science advances},
year = {2026},
month = apr,
volume = {12},
number = {15},
pages = {eady2696},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/
url = {https://
pmid = {41950316},
pmcid = {PMC13060595}
}
RIS
TY - JOUR
AU - Thakur, Abhimanyu
AU - Zhang, Kui
AU - Chen, Jonathan
AU - Mei, Shuya
AU - Chen, Jace
AU - Verdiell, Apolline
AU - Jacobs, Emily
AU - Mulder, Liza
AU - Whitford, Abigail
AU - Iyaswamy, Ashok
AU - Chen, Ya-Wen
AU - Cliffe, Anna
AU - Esser-Kahn, Aaron
AU - Chen, Bohao
AU - Lian, Qizhou
AU - Solway, Julian
AU - Xing, Shunpeng
AU - Chen, Huanhuan Joyce
TI - Pulmonary neuroendocrine cell-derived exosomes regulate iron homeostasis and oxidative stress in lung neurons
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/
VL - 12
IS - 15
SP - eady2696
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/
UR - https://
LA - en
ER -
CSL-JSON
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