机构：[1]Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR.[2]Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR.[3]Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR.[4]Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.[5]Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.[6]Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR.[7]Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR.[8]State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 651 Dongfeng East Road, Guangzhou, Guangdong Province 510060, China.[9]College of Pharmacy, Jinan Uni- versity, Guangzhou, China.[10]Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.[11]Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR.[12]Reproduction,[13]Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases, The Chinese University of Hong Kong, 999077 Hong Kong SAR.
Tumor innervation is a common phenomenon with unknown mechanism. Here, we discovered a direct mechanism of tumor-associated macrophage (TAM) for promoting de novo neurogenesis via a subset showing neuronal phenotypes and pain receptor expression associated with cancer-driven nocifensive behaviors. This subset is rich in lung adenocarcinoma associated with poorer prognosis. By elucidating the transcriptome dynamics of TAM with single-cell resolution, we discovered a phenomenon "macrophage to neuron-like cell transition" (MNT) for directly promoting tumoral neurogenesis, evidenced by macrophage depletion and fate-mapping study in lung carcinoma models. Encouragingly, we detected neuronal phenotypes and activities of the bone marrow-derived MNT cells (MNTs) in vitro. Adoptive transfer of MNTs into NOD/SCID mice markedly enhanced their cancer-associated nocifensive behaviors. We identified macrophage-specific Smad3 as a pivotal regulator for promoting MNT at the genomic level; its disruption effectively blocked the tumor innervation and cancer-dependent nocifensive behaviors in vivo. Thus, MNT may represent a precision therapeutic target for cancer pain.
基金：
This study was supported
by Research Grants Council of Hong Kong (14106518, 14111019, and 14111720), RGC
Postdoctoral Fellowship Scheme (PDFS2122-4S06), The Chinese University of Hong Kong’s
Faculty Innovation Award (4620528), Direct Grant for Research (4054510 and 4054668), and
Postdoctoral Fellowship Scheme 2021-22 (NL/LT/PDFS2022/0360/22lt).
第一作者机构：[1]Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Tang Philip Chiu-Tsun,Chung Jeff Yat-Fai,Liao Jinyue,et al.Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain[J].SCIENCE ADVANCES.2022,8(40):doi:10.1126/sciadv.abn5535.
APA：
Tang Philip Chiu-Tsun,Chung Jeff Yat-Fai,Liao Jinyue,Chan Max Kam-Kwan,Chan Alex Siu-Wing...&Tang Patrick Ming-Kuen.(2022).Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain.SCIENCE ADVANCES,8,(40)
MLA：
Tang Philip Chiu-Tsun,et al."Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain".SCIENCE ADVANCES 8..40(2022)
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