北京大学张泽民等研究人员合作发现，跨组织人类成纤维细胞图谱揭示具有不同免疫调节作用的肌成纤维细胞亚型。该研究于2024年9月19日在线发表于国际一流学术期刊《癌细胞》。

研究人员对来自517个人类样本的成纤维细胞进行了全面的单细胞RNA测序分析，样本涵盖11种组织类型和不同的病理状态。研究人员鉴定了具有普遍性和组织特异性特征的不同成纤维细胞亚群。病理状况导致成纤维细胞组成发生显著变化，包括炎症过程中免疫调节成纤维细胞的扩展以及癌症中组织重塑肌成纤维细胞的增加。

在肌成纤维细胞类别中，研究人员鉴定了来自不同发育来源的四个转录上独特的亚群，其中LRRC15⁺肌成纤维细胞表现出终末分化特征。LRRC15⁺和MMP1⁺肌成纤维细胞展示了促进肿瘤的潜力，助长了免疫排斥和免疫抑制的肿瘤微环境（TME），而PI16⁺成纤维细胞在邻近非癌区域表现出潜在的抗肿瘤功能。

成纤维细胞亚型的组成定义了具有不同临床结果的患者亚型。该研究推进了对成纤维细胞生物学的理解，并为癌症治疗中靶向特定成纤维细胞亚群提供了潜在的治疗策略。

据了解，成纤维细胞以其功能多样性著称，在炎症和癌症中发挥关键作用。

附：英文原文

Title: Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation

Author: Yang Gao, Jianan Li, Wenfeng Cheng, Tian Diao, Huilan Liu, Yufei Bo, Chang Liu, Wei Zhou, Minmin Chen, Yuanyuan Zhang, Zhihua Liu, Weidong Han, Rufu Chen, Jirun Peng, Linnan Zhu, Wenhong Hou, Zemin Zhang

Issue&Volume: 2024-09-19

Abstract: Fibroblasts, known for their functional diversity, play crucial roles in inflammation and cancer. In this study, we conduct comprehensive single-cell RNA sequencing analyses on fibroblast cells from 517 human samples, spanning 11 tissue types and diverse pathological states. We identify distinct fibroblast subpopulations with universal and tissue-specific characteristics. Pathological conditions lead to significant shifts in fibroblast compositions, including the expansion of immune-modulating fibroblasts during inflammation and tissue-remodeling myofibroblasts in cancer. Within the myofibroblast category, we identify four transcriptionally distinct subpopulations originating from different developmental origins, with LRRC15+ myofibroblasts displaying terminally differentiated features. Both LRRC15+ and MMP1+ myofibroblasts demonstrate pro-tumor potential that contribute to the immune-excluded and immune-suppressive tumor microenvironments (TMEs), whereas PI16+ fibroblasts show potential anti-tumor functions in adjacent non-cancerous regions. Fibroblast-subtype compositions define patient subtypes with distinct clinical outcomes. This study advances our understanding of fibroblast biology and suggests potential therapeutic strategies for targeting specific fibroblast subsets in cancer treatment.

DOI: 10.1016/j.ccell.2024.08.020

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00319-2