Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

Miaomiao Yang; Qiang Fan; Tom K Hei; Guodong Chen; Wei Cao; Gang Meng; Wei Han

doi:10.3390/antiox11081457

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

Antioxidants (Basel). 2022 Jul 26;11(8):1457. doi: 10.3390/antiox11081457.

Authors

Miaomiao Yang^{1

2

3}, Qiang Fan^{1

2}, Tom K Hei⁴, Guodong Chen¹, Wei Cao^{1

2}, Gang Meng³, Wei Han^{1

5}

Affiliations

¹ Anhui Province Key Laboratory of Medical Physics and Technology/Institute of Health and Medical Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, Hefei 230031, China.
² Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230026, China.
³ Clinical Pathology Center, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
⁴ Center for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, NY 10032, USA.
⁵ Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.

Abstract

Radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), is a common clinical complication associated with thoracic radiotherapy for malignant tumors. However, the specific contributions of each cell subtype to this process are unknown. Here, we provide the single-cell pathology landscape of the RP in a mouse model by unbiased single-cell RNA-seq (scRNA-seq). We found a decline of type 2 alveolar cells in the RP lung tissue, with an expansion of macrophages, especially the Fabp4low and Spp1high subgroup, while Fabp4high macrophages were almost depleted. We observed an elevated expression of multiple mitochondrial genes in the RP group, indicating a type 2 alveolar cell (AT2) response to oxidative stress. We also calculated the enrichment of a cGAS-STING signaling pathway, which may be involved in regulating inflammatory responses and cancer progression in AT2 cells of PR mice. We delineate markers and transcriptional states, identify a type 2 alveolar cell, and uncover fundamental determinants of lung fibrosis and inflammatory response in RP lung tissue of mice.

Keywords: mouse; oxidative stress; radiation pneumonitis (RP); single-cell RNA-seq (scRNA-seq).

Grants and funding

This research was supported by the National Natural Science Foundation of China (Nos. 81974484, U20A20372), Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology (No. 2019HSC-CIP010), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection.