Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.
Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.
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祖细胞和成熟人类星形胶质细胞的纯化和表征揭示了小鼠的转录和功能差异。
DOI：
10.1016/j.neuron.2015.11.013
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发表时间：
2016-01-06
期刊：
影响因子：
16.2
通讯作者：
Barres BA
中科院分区：
文献类型：
--
作者：
Zhang Y;Sloan SA;Clarke LE;Caneda C;Plaza CA;Blumenthal PD;Vogel H;Steinberg GK;Edwards MS;Li G;Duncan JA 3rd;Cheshier SH;Shuer LM;Chang EF;Grant GA;Gephart MG;Barres BA
人类和小鼠星形胶质细胞之间的功能和分子相似性和区别知之甚少。在这里，我们报告了一种免疫淘洗方法的发展，以急性纯化星形胶质细胞从胎儿，青少年和成年人的大脑，并保持这些细胞在无血清培养。我们发现人类星形胶质细胞在促进神经元存活、诱导功能性突触形成和吞噬突触体方面与小鼠星形胶质细胞具有相似的能力。与小鼠中现有的观察结果相反，我们发现成熟的人类星形胶质细胞对谷氨酸的反应强烈。接下来，我们对健康人星形胶质细胞沿着来自癫痫和肿瘤病灶的星形胶质细胞进行RNA测序，并将其与人神经元、少突胶质细胞、小胶质细胞和内皮细胞进行比较。通过这些图谱，我们鉴定了新型人类特异性星形胶质细胞基因，并发现了星形胶质细胞前体细胞和成熟有丝分裂后星形胶质细胞之间的全转录组转化。这些数据代表了健康和患病人脑的一些第一个细胞类型特异性分子谱。
The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains, and to maintain these cells in serum-free cultures. We found that human astrocytes have similar abilities to murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. We next performed RNA-sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci, and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells. With these profiles, we identified novel human-specific astrocyte genes, and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell type-specific molecular profiles of the healthy and diseased human brain.