Cells isolated from the epidermis by Hoechst dye exclusion, small size, and negative selection for hematopoietic markers can generate B lymphocyte precursors.
Cells isolated from the epidermis by Hoechst dye exclusion, small size, and negative selection for hematopoietic markers can generate B lymphocyte precursors.
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DOI：
10.1038/sj.jid.5701202
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发表时间：
2008-06
期刊：
影响因子：
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通讯作者：
Mathew M Stern;L. Tygrett;T. Waldschmidt;J. Bickenbach
中科院分区：
文献类型：
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作者：
Mathew M Stern;L. Tygrett;T. Waldschmidt;J. Bickenbach
转分化已经成为对体细胞干细胞的一种普遍主张，然而这些细胞如何能够定向到特定的细胞谱系还没有得到很好的研究。我们之前证明，当分离的表皮干细胞被置于胚胎环境中时，它们的潜力扩展到角质细胞谱系之外。在这里，我们提供的证据表明，使用我们发表的表皮干细胞方法的修改分离的细胞可以特异性地定向分化为B淋巴细胞前体。我们发现这些分离细胞与S17骨髓基质细胞在补充细胞因子的培养基中共培养，改变了细胞表面标记谱和基因表达模式，具有B淋巴细胞前体的一个特征。这些细胞也经历了可变、多样性，在免疫球蛋白重链位点加入重排，这是淋巴细胞特有的永久性遗传变化。这一特征仅限于使用改良的表皮干细胞方法分离的细胞，因为使用改良的转运扩增细胞方法分离的细胞不能被重定向或重编程。这些结果表明，来自表皮的细胞可以被引导跨越谱系界限成为中胚层来源的淋巴细胞。
Transdifferentiation has become a common claim for somatic stem cells, yet how such cells can be directed toward a specified cell lineage has not been well investigated. We previously demonstrated that when isolated epidermal stem cells were placed into an embryonic environment, their potential was extended beyond the keratinocyte lineage. Here, we present evidence that cells isolated using a modification of our published method for epidermal stem cells can be specifically directed to differentiate into B lymphocyte precursors. We found that these isolated cells co-cultured with S17 bone marrow stromal cells in cytokine-supplemented medium changed their cell surface marker profile and gene expression pattern to one characteristic of B lymphocyte precursors. Such cells also underwent variable, diversity, joining rearrangement at the immunoglobulin heavy-chain locus, a permanent genetic change unique to lymphocytes. This feature is limited to the cells isolated using the modified epidermal stem cell method, as cells isolated using the modified transit amplifying cell method could not be re-directed or reprogrammed. Such results demonstrate that cells from the epidermis can be directed to cross lineage boundaries to become mesodermally derived lymphocytes.