Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis
Summary: Male infertility is a global health problem especially prevalent in high-altitude regions. The epididymis is essential for sperm maturation, but the influence of environmental cues on its reshaping remains poorly understood. Here, we use single-cell transcriptomics to track the cellular pro...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723014547 |
| _version_ | 1797448075319443456 |
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| author | Jitao Zeng Weiwu Gao Ying Tang Ying Wang Xiaona Liu Jun Yin Xingxing Su Mengjie Zhang Enchuan Kang Yi Tian Bing Ni Wei He |
| author_facet | Jitao Zeng Weiwu Gao Ying Tang Ying Wang Xiaona Liu Jun Yin Xingxing Su Mengjie Zhang Enchuan Kang Yi Tian Bing Ni Wei He |
| author_sort | Jitao Zeng |
| collection | DOAJ |
| description | Summary: Male infertility is a global health problem especially prevalent in high-altitude regions. The epididymis is essential for sperm maturation, but the influence of environmental cues on its reshaping remains poorly understood. Here, we use single-cell transcriptomics to track the cellular profiles of epidydimal cells in rats raised under normoxia or extended hypoxia. The results show that hypoxia impairs epididymal function, evident in reduced epithelial cells, compromised blood-epididymis barrier integrity, and increased natural killer cells. Through combined analysis of gene-regulatory networks and cell-cell interaction maps, we identify epididymal hypoxia-sensitive cells that communicate with natural killer (NK) cells via increased intercellular adhesion molecule 1 (ICAM-1) driven by KLF4 recruitment of the histone methyltransferase ASL1L to the Icam1 promoter. Taken together, our study offers a detailed blueprint of epididymal changes during hypoxia and defines a KLF4-ALSH1L-ICAM-1 axis contributing to NK cell activation, yielding a potential treatment targeting hypoxia-induced infertility. |
| first_indexed | 2024-03-09T14:05:08Z |
| format | Article |
| id | doaj.art-bb4513a721884a41b10100668d2e6f71 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:05:08Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bb4513a721884a41b10100668d2e6f712023-11-30T05:07:16ZengElsevierCell Reports2211-12472023-11-014211113442Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymisJitao Zeng0Weiwu Gao1Ying Tang2Ying Wang3Xiaona Liu4Jun Yin5Xingxing Su6Mengjie Zhang7Enchuan Kang8Yi Tian9Bing Ni10Wei He11Reproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, ChinaInstitute of Immunology, People’s Liberation Army (PLA), and Department of Immunology, College of Basic Medicine, Army Medical University, Chongqing, ChinaReproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, ChinaReproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, ChinaReproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Pathophysiology, College of High-Altitude Military Medicine, Army Medical University, Chongqing, ChinaHepatological Surgery Department, Southwest Hospital, Army Medical University, Chongqing, ChinaDepartment of Pathophysiology, College of High-Altitude Military Medicine, Army Medical University, Chongqing, ChinaReproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, ChinaInstitute of Immunology, People’s Liberation Army (PLA), and Department of Immunology, College of Basic Medicine, Army Medical University, Chongqing, ChinaDepartment of Pathophysiology, College of High-Altitude Military Medicine, Army Medical University, Chongqing, ChinaReproductive Medical Center, Southwest Hospital, Army Medical University, Chongqing, China; Corresponding authorSummary: Male infertility is a global health problem especially prevalent in high-altitude regions. The epididymis is essential for sperm maturation, but the influence of environmental cues on its reshaping remains poorly understood. Here, we use single-cell transcriptomics to track the cellular profiles of epidydimal cells in rats raised under normoxia or extended hypoxia. The results show that hypoxia impairs epididymal function, evident in reduced epithelial cells, compromised blood-epididymis barrier integrity, and increased natural killer cells. Through combined analysis of gene-regulatory networks and cell-cell interaction maps, we identify epididymal hypoxia-sensitive cells that communicate with natural killer (NK) cells via increased intercellular adhesion molecule 1 (ICAM-1) driven by KLF4 recruitment of the histone methyltransferase ASL1L to the Icam1 promoter. Taken together, our study offers a detailed blueprint of epididymal changes during hypoxia and defines a KLF4-ALSH1L-ICAM-1 axis contributing to NK cell activation, yielding a potential treatment targeting hypoxia-induced infertility.http://www.sciencedirect.com/science/article/pii/S2211124723014547CP: Immunology |
| spellingShingle | Jitao Zeng Weiwu Gao Ying Tang Ying Wang Xiaona Liu Jun Yin Xingxing Su Mengjie Zhang Enchuan Kang Yi Tian Bing Ni Wei He Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis Cell Reports CP: Immunology |
| title | Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis |
| title_full | Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis |
| title_fullStr | Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis |
| title_full_unstemmed | Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis |
| title_short | Hypoxia-sensitive cells trigger NK cell activation via the KLF4-ASH1L-ICAM-1 axis, contributing to impairment in the rat epididymis |
| title_sort | hypoxia sensitive cells trigger nk cell activation via the klf4 ash1l icam 1 axis contributing to impairment in the rat epididymis |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723014547 |
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