Towards a transcriptome definition of microglial cells
Towards a transcriptome definition of microglial cells
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DOI：
10.1007/s10048-004-0172-5
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发表时间：
2004-06-01
期刊：
影响因子：
2.2
通讯作者：
Graeber, MB
中科院分区：
文献类型：
--
作者：
Moran, LB;Duke, DC;Graeber, MB
本研究提供了干扰素-γ（IFN-γ）激活的小胶质细胞的表达特征。小胶质细胞是存在于脑和脊髓中的巨噬细胞前体细胞。小胶质细胞表型是高度可塑的，并且响应于许多病理刺激而变化。IFN-γ在体外和体内均被确定为小胶质细胞的强免疫激活剂。使用AffyR RG_U34 A微阵列来确定IFN-γ刺激对从新生刘易斯大鼠脑分离的小胶质细胞的影响。超过8，000个基因序列被检查，即，7,000个已知基因和1,000个表达序列标签（EST）簇。在基线条件下，小胶质细胞表达了8,000个基因中的326个（约占所有基因的4%，182个已知基因和144个EST）。IFN-γ刺激仅诱导了7,000个已知基因中的34个和1,000个EST中的8个的转录。大多数新表达的基因编码促炎细胞因子和MHC介导的抗原呈递途径的组分。IFN-γ使182个已鉴定基因中的60个和144个ESTs中的9个的表达增加，而IFN-γ刺激培养物中182个已知基因中的29个和144个ESTs中的7个下调或检测不到。总体而言，IFN-γ对小胶质细胞转录组的激活作用显示出对参与抗原呈递、蛋白质降解、肌动蛋白结合、细胞粘附、细胞凋亡和细胞信号传导的途径的限制。相比之下，IFN-γ刺激的下调作用似乎仅限于生长调节、细胞外基质重塑、脂质代谢和溶酶体加工的途径。此外，转录组分析揭示了先前未知的小胶质细胞基因，这些基因被重新表达，如钙调蛋白3，或指示差异调节反应，如下调组织蛋白酶，这些组织蛋白酶响应于其他小胶质细胞刺激物而上调。
This study provides an expression signature of interferon-gamma (IFN-gamma)-activated microglia. Microglia are macrophage precursor cells residing in the brain and spinal cord. The microglial phenotype is highly plastic and changes in response to numerous pathological stimuli. IFN-gamma has been established as a strong immunological activator of microglial cells both in vitro and in vivo. Affymetrix RG_U34A microarrays were used to determine the effect of IFN-gamma stimulation on migroglia cells isolated from newborn Lewis rat brains. More than 8,000 gene sequences were examined, i.e., 7,000 known genes and 1,000 expressed sequence tag (EST) clusters. Under baseline conditions, microglia expressed 326 of 8,000 genes examined (approximately 4% of all genes, 182 known and 144 ESTs). Transcription of only 34 of 7,000 known genes and 8 of 1,000 ESTs was induced by IFN-gamma stimulation. The majority of the newly expressed genes encode pro-inflammatory cytokines and components of the MHC-mediated antigen presentation pathway. The expression of 60 of 182 identified genes and of 9 of 144 ESTs was increased by IFN-gamma, whereas 29 of 182 known genes and 7 of 144 ESTs were down-regulated or undetectable in IFN-gamma-stimulated cultures. Overall, the activating effect of IFN-gamma on the microglial transcriptome showed restriction to pathways involved in antigen presentation, protein degradation, actin binding, cell adhesion, apoptosis, and cell signaling. In comparison, down-regulatory effects of IFN-gamma stimulation appeared to be confined to pathways of growth regulation, remodeling of the extracellular matrix, lipid metabolism, and lysosomal processing. In addition, transcriptomic profiling revealed previously unknown microglial genes that were de novo expressed, such as calponin 3, or indicated differential regulatory responses, such as down-regulation of cathepsins that are up-regulated in response to other microglia stimulators.