Genome-wide analysis reveals the unique stem cell identity of human amniocytes.
Genome-wide analysis reveals the unique stem cell identity of human amniocytes.
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DOI：
10.1371/journal.pone.0053372
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Condic ML
中科院分区：
文献类型：
--
作者：
Maguire CT;Demarest BL;Hill JT;Palmer JD;Brothman AR;Yost HJ;Condic ML
人类羊水中含有可能具有重要干细胞特征的细胞，但控制其发育潜能的程序尚不清楚。在这里，我们提供的证据表明，来源于多个患者的单核细胞的多能性标志物的表达水平的异质性和变异性。来自多个患者的克隆分析表明，巨噬细胞具有大量的自我更新细胞，这些细胞具有产生具有多能标记物异质性的独特巨噬细胞表型的固有特性。对于其治疗潜力重要的是，全基因组谱在不同的胎龄和培养时间是不同的，但在性别之间没有差异。基于整个转录组的分级聚类和差异表达分析，巨噬细胞表达与多能性和干细胞抑制相关的典型调节因子。它们的特征与人胚胎干细胞（ESC）、诱导多能干细胞（iPSC）和新生儿包皮成纤维细胞不同。羊膜细胞具有复杂的分子特征，共表达滋养层、外胚层、中胚层和内胚层细胞类型特异性调节因子。与目前对干细胞基态的看法相反，ESC和iPSC还表达高水平的广泛的细胞类型特异性调节剂。多谱系分化标志物的共表达与ES细胞阻遏物的子集在巨噬细胞中的强表达相结合，表明这些细胞具有不同于任何其他已知细胞类型或谱系的独特表型。
Human amniotic fluid contains cells that potentially have important stem cell characteristics, yet the programs controlling their developmental potency are unclear. Here, we provide evidence that amniocytes derived from multiple patients are marked by heterogeneity and variability in expression levels of pluripotency markers. Clonal analysis from multiple patients indicates that amniocytes have large pools of self-renewing cells that have an inherent property to give rise to a distinct amniocyte phenotype with a heterogeneity of pluripotent markers. Significant to their therapeutic potential, genome-wide profiles are distinct at different gestational ages and times in culture, but do not differ between genders. Based on hierarchical clustering and differential expression analyses of the entire transcriptome, amniocytes express canonical regulators associated with pluripotency and stem cell repression. Their profiles are distinct from human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), and newborn foreskin fibroblasts. Amniocytes have a complex molecular signature, coexpressing trophoblastic, ectodermal, mesodermal, and endodermal cell-type-specific regulators. In contrast to the current view of the ground state of stem cells, ESCs and iPSCs also express high levels of a wide range of cell-type-specific regulators. The coexpression of multilineage differentiation markers combined with the strong expression of a subset of ES cell repressors in amniocytes suggests that these cells have a distinct phenotype that is unlike any other known cell-type or lineage.
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影响因子：
1.6
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作者：
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