A Novel Approach for the Derivation of Putative Primordial Germ Cells and Sertoli Cells from Human Embryonic Stem Cells
A Novel Approach for the Derivation of Putative Primordial Germ Cells and Sertoli Cells from Human Embryonic Stem Cells
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DOI：
10.1634/stemcells.2007-1018
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Montgomery, Anthony M. P.
中科院分区：
文献类型：
--
作者：
Bucay, Nathan;Yebra, Mayra;Montgomery, Anthony M. P.
我们利用人类胚胎干细胞（hESCs）描述了一种新的方法，用于快速诱导和富集与原始生殖细胞（PGCs）和支持细胞相似的细胞。所描述的方法基于对通常用于扩增hESCs的生长条件进行适度改变，且不需要基因操作或复杂的三维培养。值得注意的是，我们已经确定，仅仅减小培养的胚胎干细胞集落的大小以及控制换液周期的次数，就会导致与迁移性原始生殖细胞相似的细胞迅速出现。重要的是，可以根据趋化因子受体CXCR4的表达来监测和纯化这些细胞。在更严格的分化条件下，这些细胞会成熟并上调特定生殖细胞标志物的表达。重要的是，这一过程伴随着支持细胞样细胞的产生。这类细胞通常为发育中的生殖细胞提供营养支持和免疫保护，并且可能在预防移植物排斥方面具有重要的临床应用价值。本研究中产生的假定的支持细胞 - 生殖细胞共培养物最终可能被用于研究和操控人类配子发生所涉及的相互作用和过程。《干细胞》2009年；27卷：68 - 77页
Using human embryonic stem cells (hESCs), we describe a novel method for the rapid derivation and enrichment of cells that are comparable to primordial germ cells (PGCs) and Sertoli cells. The methodology described is based on modest changes to the growth conditions commonly used to expand hESCs and does not require genetic manipulation or complex three-dimensional culture. Remarkably, we have determined that simply reducing the size of cultured ESC colonies and manipulating the number of feeding cycles, results in the rapid emergence of cells that are comparable to migratory PGCs. Importantly, these cells can be monitored and purified on the basis of the expression of the chemokine receptor CXCR4. Under more stringent differentiating conditions these cells mature and upregulate the expression of specific germ cell markers. Importantly, this process is accompanied by the development of Sertoli-like support cells. Such cells normally provide trophic support and immunoprotection to developing germ cells and may have significant clinical utility in the prevention of graft rejection. The putative Sertoli-germ cell cocultures generated in this study may ultimately be developed to study and manipulate interactions and processes involved in human gametogenesis. STEM CELLS 2009; 27: 68-77