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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence
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Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence

机译：人表皮干细胞和转运扩增细胞的单细胞表达谱：Lrig1是干细胞静止的调节剂

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Considerable progress has been made in characterizing epidermal stem cells by microarray analysis of FACS-selected populations. One limitation of this approach is that the gene expression profiles represent the average of the cell population, potentially masking cellular heterogeneity of functional significance. To overcome this problem, we have performed single-cell expression profiling. We have generated (DNA libraries from single human epidermal cells, designated as stem or transit-amplifying cells on the basis of Delta1 and melanoma-associated chondroitin sulfate proteoglycan expression. Of the 14 putative stem cell markers identified, we selected one, the EGF receptor antagonist leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), for further study. Lrig1 was expressed in groups of basal cells in human interfollicular epidermis previously identified as enriched for stem cells. Overexpression of Lrig1 decreased keratinocyte proliferation but did not affect the proportion of stem and transit-amplifying cells, as judged by clonal growth characteristics. Down-regulation of Lrig1 using siRNA increased cell-surface EGF receptor levels, enhanced activation of downstream pathways, and stimulated proliferation. Lrig1 acted in part by negatively regulating the Myc promoter. We propose that Lrig1 maintains epidermal stem cells in a quiescent nondividing state, and that Lrig1 down-regulation triggers proliferation.
机译：通过对FACS选择的人群进行微阵列分析，在表征表皮干细胞方面已经取得了可观的进展。该方法的局限性在于基因表达谱代表细胞群体的平均值，可能掩盖了具有功能重要性的细胞异质性。为了克服这个问题，我们进行了单细胞表达谱分析。我们已经从Delta1和黑色素瘤相关的硫酸软骨素蛋白聚糖表达的基础上，从单个人表皮细胞（称为干细胞或转运扩增细胞）生成了DNA文库。在鉴定出的14种推定干细胞标记中，我们选择了一种，即EGF受体富含亮氨酸的拮抗剂重复序列和免疫球蛋白样结构域1（Lrig1），用于进一步研究：Lrig1在先前确定为干细胞富集的人小泡间表皮基底细胞群中表达； L​​rig1的过表达降低了角质形成细胞的增殖，但并未影响通过克隆生长特性判断，干细胞和转运扩增细胞的比例；使用siRNA下调Lrig1会增加细胞表面EGF受体水平，增强下游通路的激活并刺激增殖； Lrig1的部分作用是通过负调控Myc来实现的。我们建议Lrig1将表皮干细胞维持在静止的不分裂状态，并且Lrig1下调触发增殖。

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