biostudies-literatureUnknown8(40)Tang PCTumor 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 MNTsScience advanceseabn5535https://www.ebi.ac.uk/biostudies/studies/S-EPMC9544324biostudies-literatureSingle-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain.PMC9544324Lan HYChan ASLee TLTang PCLam EWZhang DLi CLeung KTNg CSChan MKKo HLiao JTo KFJiang XHo YPTang PMCheng GHuang XRChung JYfalseSingle-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain.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 MNTs2022-01-01T00:00:00Z2022 Oct2025-04-22T10:38:07.414Z2025-02-18T23:58:15.896ZS-EPMC95443243620634310.1126/sciadv.abn5535