COPD 患者和对照者骨髓、脂肪组织和肺组织间充质基质细胞中的基因表达谱。
Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls.
机构信息
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, Groningen, The Netherlands.
Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
出版信息
Respir Res. 2023 Jan 21;24(1):22. doi: 10.1186/s12931-023-02314-8.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients.
AIM
To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls.
METHODS
We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq).
RESULTS
We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene.
CONCLUSION
Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes.
背景
慢性阻塞性肺疾病（COPD）的特征是肺组织的不可逆损伤。目前迫切需要新的再生策略。培养的间充质干细胞（MSCs）在 COPD 实验模型中显示出有希望的结果，但来源的差异可能会影响其在患者治疗策略中的潜在用途。
目的
评估来自 COPD 患者和非 COPD 对照的肺源性间充质干细胞（LMSCs）、骨髓源性间充质干细胞（BM-MSCs）和脂肪源性间充质干细胞（AD-MSCs）的转录组。
方法
我们使用 RNA 测序（RNA-seq）研究了 MSC 亚型之间以及 COPD 和对照之间的基因表达谱差异。
结果
我们表明，除了供体之间的异质性外，不同来源的 MSC 具有强烈的发散基因特征。生长因子 FGF10 和 HGF 主要在 LMSCs 中表达。来自所有来源的 MSC 在 COPD 中均显示出改变的表达谱，脂肪组织来源的 MSC 中最显著的上调和下调基因。通路分析表明，COPD 衍生的 AD-MSCs 中差异表达最明显的基因与细胞外基质（ECM）结合和表达有关。在 LMSCs 中，COPD 和对照之间差异最显著的基因是 CSGALNACT1，这是一种调节 ECM 的基因。
结论
来自 COPD 患者的自体 MSC 表现出与转录组相关的异常，其中最明显的是来自肺外来源的 MSC。由于特定生长因子基因的表达，LMSCs 可能最适合肺组织修复。
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