单细胞 RNA 序列测定发现骨髓衍生的祖细胞是多种器官纤维化疾病细胞外基质生成细胞的主要来源。

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2024-09-16 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.98839
Yu Zhong, Biao Wei, Wenbiao Wang, Junzhe Chen, Wenjing Wu, Liying Liang, Xiao-Ru Huang, Cheuk-Chun Szeto, Xueqing Yu, David J Nikolic-Paterson, Hui-Yao Lan
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引用次数: 0

摘要

纤维化的特点是由于组织修复反应失调导致细胞外基质(ECM)异常沉积,给纤维化相关疾病造成了巨大的全球性负担。虽然表达α-平滑肌肌动蛋白(α-SMA/ACTA2)的肌成纤维细胞被认为是纤维化过程中的关键角色,但 ECM 生成细胞的来源仍存在争议。为了解决这个问题,我们整合并分析了大规模单细胞转录组数据集,这些数据集来自患有不同纤维化疾病的患者,涉及心脏、肺、肝脏或肾脏。意想不到的是,并非所有表达 ACTA2 的细胞都是通过表达胶原基因鉴定的 ECM 生成细胞;相反,在所有纤维化疾病中,大多数 ECM 生成细胞都是来源于循环骨髓前体的肌成纤维细胞和成纤维细胞,少量来源于局部周细胞和血管平滑细胞。在性别不匹配的肾脏移植中发现,产生 ECM 的细胞来源于受体而非供体的骨髓来源祖细胞(BMPCs),从而证实了这一点。此外,这些源自 BMPCs 的 ECM 生成细胞表现出一种促炎表型。因此,具有干细胞特性的骨髓源性促炎症和坏死性成纤维细胞/肌成纤维细胞是ECM生成细胞的主要来源,可能在多种人类纤维化疾病的组织纤维化中起着推动作用。以这些产生 ECM 的细胞为靶标,可为纤维化疾病提供一种新型疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-Cell RNA-Sequencing Identifies Bone Marrow-Derived Progenitor Cells as a Main Source of Extracellular Matrix-Producing Cells Across Multiple Organ-Based Fibrotic Diseases.

Fibrosis is characterized by the aberrant deposition of extracellular matrix (ECM) due to dysregulated tissue repair responses, imposing a significant global burden on fibrosis-related diseases. Although alpha-smooth muscle actin (α-SMA/ACTA2)-expressing myofibroblasts are considered as key player in fibrogenesis, the origin of ECM-producing cells remains controversial. To address this issue, we integrated and analyzed large-scale single-cell transcriptomic datasets from patients with distinct fibrotic diseases involving the heart, lung, liver, or kidney. Unexpectedly, not all ACTA2-expressing cells were ECM-producing cells identified by expressing collagen genes; instead, the majority of ECM-producing cells were myofibroblasts and fibroblasts derived from circulating bone marrow precursor, and to a lesser extent from local pericytes and vascular smooth cells in all fibrotic diseases. This was confirmed in sex-mismatched kidney transplants by the discovery that ECM-producing cells originated from recipient, not donor, bone marrow-derived progenitor cells (BMPCs). Moreover, these BMPCs-derived ECM-producing cells exhibited a proinflammatory phenotype. Thus, bone marrow-derived proinflammatory and profibrotic fibroblasts/myofibroblasts with stem cell properties serve as a major source of ECM-producing cells and may play a driving role in tissue fibrosis across a wide range of human fibrotic diseases. Targeting these ECM-producing cells may provide a novel therapy for diseases with fibrosis.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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