Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human
Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human
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DOI：
10.1002/dvdy.20034
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发表时间：
2004-05-01
影响因子：
2.5
通讯作者：
Robb, L
中科院分区：
文献类型：
--
作者：
Hart, AH;Hartley, L;Robb, L
小鼠Nanog基因是DNA结合转录因子同源框家族的成员，最近已被证明可以维持胚胎干细胞的多能性。我们已经使用了序列同源性和表达筛选来识别和克隆小鼠和人Nanog基因，并表征了它们的系统发育背景和表达模式。我们在这里报告的基因结构和表达模式的小鼠Nanog基因，人类Nanog和Nanog2基因，和六个加工的人类Nanog假基因。小鼠Nanog表达在未分化的胚胎干细胞中高，并且在胚胎干细胞分化期间下调，伴随着多能性的丧失。在胚泡的内细胞团中检测到鼠胚胎Nanog表达。植入后，Nanog可在胚胎第6天（E）在假定原始条纹区域的近端外胚层中检测到。在原肠胚形成过程中，随着条纹的延长，表达向远端延伸，并且仍然局限于上胚层。Nanog RNA在通过条纹进入以形成中胚层和定形内胚层的细胞中下调。Nanog表达也标志着E11.5-E12.5的新生性腺的多能生殖细胞，并且在生殖细胞肿瘤和畸胎瘤衍生的细胞系中高度表达。逆转录-聚合酶链反应分析检测到小鼠Nanog在几个成年组织中的低水平表达。人类Nanog基因在胚胎干细胞中表达，并在所有成体组织和分化细胞系中下调。通过北方分析在未分化的N-Tera胚胎癌细胞系中检测到高水平的人Nanog表达。小鼠和人Nanog和Nanog2基因的基因序列、结构和表达的保守性可能反映了在两个物种中维持多能性的共同作用。(C)2004威利-利斯公司
The murine Nanog gene, a member of the homeobox family of DNA binding transcription factors, has been shown recently to maintain pluripotency of embryonic stem cells. We have used a sequence homology and expression screen to identify and clone the mouse and human Nanog genes and characterized their phylogenetic context and expression patterns. We report here the gene structure and expression patterns of the mouse Nanog gene, the human Nanog and Nanog2 genes, and six processed human Nanog pseudogenes. Mouse Nanog expression is high in undifferentiated embryonic stem cells and is down-regulated during embryonic stem cell differentiation, concomitant with loss of pluripotency. Murine embryonic Nanog expression is detected in the inner cell mass of the blastocyst. After implantation, Nanog is detectable at embryonic day (E) 6 in proximal epiblast in the region of the presumptive primitive streak. Expression extends distally as the streak elongates during gastrulation and remains restricted to epiblast. Nanog RNA is down-regulated in cells ingressing through the streak to form mesoderm and definitive endoderm. Nanog expression also marks the pluripotent germ cells of the nascent gonad at E11.5-E12.5 and is highly expressed in germ cell tumour and teratoma-derived cell lines. Reverse transcriptase-polymerase chain reaction analysis detected mouse Nanog expression at low levels in several adult tissues. The human Nanog genes are expressed in embryonic stem cells and down-regulated in all adult tissues and differentiated cell lines examined. High levels of human Nanog expression were detected by Northern analysis in the undifferentiated N-Tera embryonal carcinoma cell line. The conservation in gene sequence, structure, and expression of mouse and human Nanog and Nanog2 genes may reflect a common role in the maintenance of pluripotency in both species. (C) 2004 Wiley-Liss, Inc.