Liu Jun, Higgins Claire A, Whitehouse Jenna C, Harris Susan J, Crawford Heather, Christiano Angela M, Lako Majlinda, Hole Nicholas, Jahoda Colin A B
Department of Biosciences, Durham University, Durham DH1 3LE, UK.
Department of Dermatology, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA.
Stem Cells Int. 2018 Aug 2;2018:8631432. doi: 10.1155/2018/8631432. eCollection 2018.
In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications.
在毛囊中,真皮乳头(DP)和真皮鞘(DS)支持并维持产生毛发纤维的上皮干细胞的增殖和分化。鉴于它们的调节特性,在本研究中,我们调查了毛囊真皮细胞(DP和DS)与胚胎干细胞(ESC)、诱导多能干细胞(iPSC)以及造血干细胞之间的相互作用。我们发现,通过分化分析、免疫细胞化学以及针对未分化ESC标志物的逆转录聚合酶链反应(RT-PCR)确定,毛囊真皮细胞与ESC或iPSC共培养可支持它们在明显未分化状态下的长期维持。我们进一步表明,参与支持ESC的细胞因子也由培养的毛囊真皮细胞表达,这为共培养中ES细胞干性的维持提供了一种可能的解释。相同的细胞因子在毛囊内的表达模式,与其在毛囊生长活动中的作用比在干细胞维持中的作用更为一致。最后,我们表明,在已建立的共培养模型中,培养的小鼠毛囊真皮细胞为造血提供了良好的基质支持。人毛囊真皮细胞是多能细胞和造血细胞易于获取且易于增殖的饲养层细胞来源,具有临床应用潜力。