Human neural crest cells display molecular and phenotypic hallmarks of stem cells.

Human neural crest cells display molecular and phenotypic hallmarks of stem cells.
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DOI:
10.1093/hmg/ddn235
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发表时间:
2008-11-01
影响因子:
3.5
通讯作者:
Etchevers HC
Etchevers HC
中科院分区:
生物学2区
文献类型:
--
作者:
Thomas S;Thomas M;Wincker P;Babarit C;Xu P;Speer MC;Munnich A;Lyonnet S;Vekemans M;Etchevers HC

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发育和干细胞生物学领域都在探索如何从自我更新的创始群体中产生功能不同的细胞类型。多能、增殖的人类神经嵴细胞(hNCC)在怀孕第一个月末发育。据推测,大多数神经嵴干细胞在整个生物体迁移后分化,尽管在动物模型中,据报道神经嵴干细胞在出生后组织中持续存在。随着时间的推移,从侵袭性间质到分化后代(如背根神经节、上颌骨或肾上腺髓质)的分子通路在许多先天性疾病中发生改变。为了确定这些通路的其他成分,我们从咽部获得并维持了自我更新的hNCC系。我们发现,与动物不同,hNCC能够在无饲料条件下自我更新。虽然跨物种比较显示人类、小鼠和鸟类NCC转录组之间存在广泛的重叠,但一些分子级联仅在人类细胞中活跃,与表型差异相关。此外,我们发现,与其他干细胞群体或hNCC衍生物相比,全球hNCC分子图谱与多能胚胎干细胞高度相似。多能性标记NANOG, POU5F1和SOX2也在hNCC中表达,并且一小部分转录本可以明确地将hNCC与其他细胞类型区分开来。因此,hNCC分子特征是独特的,也是未承诺干细胞的整体特征。
The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating throughout the organism, although in animal models neural crest stem cells reportedly persist in postnatal tissues. Molecular pathways leading over time from an invasive mesenchyme to differentiated progeny such as the dorsal root ganglion, the maxillary bone or the adrenal medulla are altered in many congenital diseases. To identify additional components of such pathways, we derived and maintained self-renewing hNCC lines from pharyngulas. We show that, unlike their animal counterparts, hNCC are able to self-renew ex vivo under feeder-free conditions. While cross species comparisons showed extensive overlap between human, mouse and avian NCC transcriptomes, some molecular cascades are only active in the human cells, correlating with phenotypic differences. Furthermore, we found that the global hNCC molecular profile is highly similar to that of pluripotent embryonic stem cells when compared with other stem cell populations or hNCC derivatives. The pluripotency markers NANOG, POU5F1 and SOX2 are also expressed by hNCC, and a small subset of transcripts can unambiguously identify hNCC among other cell types. The hNCC molecular profile is thus both unique and globally characteristic of uncommitted stem cells.
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发表时间: 2007-06
期刊: Development (Cambridge, England)
影响因子: --
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