Canine Follicle Stem Cell Candidates Reside in the Bulge and Share Characteristic Features with Human Bulge Cells
Canine Follicle Stem Cell Candidates Reside in the Bulge and Share Characteristic Features with Human Bulge Cells
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DOI：
10.1038/jid.2010.68
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发表时间：
2010-08-01
影响因子：
6.5
通讯作者：
Ohyama, Manabu
中科院分区：
文献类型：
--
作者：
Kobayashi, Tetsuro;Iwasaki, Toshiroh;Ohyama, Manabu
毛囊隆起作为干细胞储存库引起了人们的极大兴趣。之前的研究主要集中在啮齿动物或人类的凸出干细胞上，而我们对其他物种的了解是有限的。在这项研究中，我们试图定位和表征犬毛囊中的候选干细胞。犬皮肤异种移植研究将标记保留细胞定位在立毛肌插入点周围的外根鞘中，在此处检测到人类凸起标记物角蛋白 15 和卵泡抑素的免疫反应性。富含犬凸起细胞的角质形成细胞上调人类凸起生物标志物 CD200 和 DIO2，并保留凸起干细胞的关键细胞调节因子，例如 SOX9 和 LHX2。重要的是，犬凸起来源的角质形成细胞在体外高度增殖，并且当与毛原性真皮细胞结合时，在体内重建毛囊皮脂腺结构和表皮。成功检测到犬类特异性 DNA 序列表明再生组织源自犬类。此外，犬特异性凸出细胞和皮脂细胞谱系标记物在重建的毛囊皮脂腺单位中表达，这意味着犬凸出细胞具有多能性。我们的研究结果证明了利用犬凸出细胞来研究人类干细胞生物学和涉及凸出区域的顽固性毛发疾病的独特策略。
The hair follicle bulge has attracted great interest as a stem cell repository. Previous studies have focused on rodent or human bulge stem cells, and our understanding of those in other species is limited. In this study, we attempted to localize and characterize stem cell candidates in canine hair follicles. The canine skin xenografting study located label-retaining cells in the outer root sheath around the insertion point of the arrector pili muscle, where the immunoreactivity of human bulge markers, keratin 15 and follistatin, were detected. Canine bulge cell-enriched keratinocytes up-regulated human bulge biomarkers CD200 and DIO2, and conserved key cell regulators of bulge stem cells, such as SOX9 and LHX2. Importantly, canine bulge-derived keratinocytes were highly proliferative in vitro and, when combined with trichogenic dermal cells, reconstituted pilosebaceous structures as well as the epidermis in vivo. Successful detection of canine specific DNA sequences suggested that the regenerated tissue was of canine origin. In addition, canine specific bulge cell and sebocyte lineage markers were expressed in reconstituted pilosebaceous units, implying the multipotency of canine bulge cells. Our findings demonstrate a unique strategy utilizing canine bulge cells to investigate human stem cell biology and intractable hair disorders that involve the bulge region.