小鼠毛囊再生与胸腺素β4的促进效应

背景:近年来研究表明,胸腺素β4与毛囊的生长发育和毛发的生长周期有着密切关系,但其作用机制尚不清楚。目的:探讨胸腺素β4通过Wnt信号通路作用于毛囊干细胞对毛囊再生的促进作用。方法:将实验小鼠随机分为低剂量胸腺素β4组、高剂量胸腺素β4组和对照组,使用松香/石蜡混合制剂建立脱毛模型。低剂量胸腺素β4组和高剂量胸腺素β4组给药浓度分别为0.3μg/50μL和3μg/50μL,对照组给予等量PBS,每隔12 h给药1次,均匀涂抹于小鼠脱毛背部。应用大体照相、苏木精-伊红染色、免疫组化及原位杂交技术,观察毛发生长情况,检测不同时间点和不同给药浓度下小鼠毛囊根部细胞β-catenin、LEF-1 mRNA的表达水平。结果与结论:低剂量胸腺素β4组毛发再生速度高于高剂量胸腺素β4组和对照组。苏木精-伊红染色显示在脱毛初期,各组小鼠真皮和皮下脂肪层有一定炎性细胞浸润,9 d时,低剂量胸腺素β4组生长期毛囊数量明显多于高剂量胸腺素β4组和对照组。免疫组织化学和原位杂交结果分别显示β-catenin和LEF-1 mRNA主要表达于毛囊隆突部和外根鞘处细胞的胞浆中,经积分吸光度分析发现低剂量胸腺素β4组阳性细胞数量和染色强度高于高剂量胸腺素β4组和对照组(P0.05),高剂量胸腺素β4组与对照组间差异无显著性意义。结果显示低剂量的胸腺素β4可以增加部分毛囊外根鞘处细胞内β-catenin和LEF-1 mRNA的表达。胸腺素β4可以促进毛囊再生的机制可能与影响Wnt信号通路有关。     

鼠胚胎期和出生后毛囊下段启动再生表达的Wnt5a

背景:Wnt5a是唯一在真皮高表达,与毛囊真皮成分发生密切相关的信号分子。目的:通过观察E12.5-E15.5胎龄的大鼠胚胎皮肤和大鼠触须毛囊上段裸鼠移植诱导毛乳头再生过程Wnt5a的表达,初步研究毛乳头胚胎发生和体外再生的启动机制。方法:将孕SD大鼠在E12.5、E13.5、E14.5、E15.5麻醉后处死,取出完整胚胎制作石蜡切片;另取单个SD大鼠触须毛囊切除毛乳头,毛囊上段拔除毛干后移植至Nu/Nu裸鼠背部皮肤;分别取以上胎龄的大鼠胚胎皮肤及裸鼠背部移植部位的毛囊标本,用酶标免疫组化法观察Wnt5a在大鼠胚胎皮肤及大鼠触须毛囊上段裸鼠移植诱导毛乳头再生过程的表达,苏木精-伊红染色观察大鼠触须毛囊上段移植后毛囊下段的再生情况。动物实验均已获得汕头大学医学院动物伦理委员会批准。结果与结论:①E12.5 Wnt5a在表皮细胞表达;E13.5 Wnt5a在表皮细胞表达增强;E14.5 Wnt5a表达由表皮转移至真皮,在真皮细胞浆明显表达;E15.5 Wnt5a表达在真皮结缔组织明显增强,在表皮的表达消失;②大鼠触须毛囊上段移植后第3天开始至第9天,毛囊上段向下形成新的毛球部,恢复完整毛囊结构,再生过程相关组织Wnt5a均呈强阳性表达;③Wnt5a在胚胎毛囊发生前后和毛囊下段再生模型毛乳头形成的部位呈现高表达,说明Wnt信号通路与毛乳头再生有密切的关系,其中Wnt5a可能扮演了非常主要的角色。     

小鼠自然毛囊生长周期及β连环蛋白的表达

目的 观察昆明系小鼠自然毛囊生长周期的组织学特点,探讨β连环蛋白(β-catenin)在小鼠自然毛囊生长周期中的表达规律及其与毛囊生长更替的关系。 方法 采用石蜡切片HE染色、Western blotting以及免疫组织化学方法,研究小鼠（90只）毛囊的周期性变化,检测β-catenin在小鼠毛囊生长不同时期皮肤组织中的蛋白表达水平,并对其进行组织定位。 结果 处于不同生长时期的毛囊具有各期的特殊结构;Western blotting结果显示,在小鼠皮肤组织粗蛋白提取物中存在分子量约为85kD且与兔抗β-catenin多克隆抗体发生免疫阳性反应的蛋白条带;免疫组织化学结果显示,β-catenin在不同毛囊生长时期的表皮、皮脂腺、根鞘和真皮乳头均有不同程度的表达。 结论 昆明系小鼠毛囊生长呈周期性变化,β-catenin在毛囊生长周期中的阳性反应与毛囊的周期性变化存在相关性,表明β-catenin在昆明系小鼠自然毛囊生长周期中起维持、促进毛囊生长的作用。     

毛囊真皮鞘细胞的生物学特性研究进展

真皮鞘包绕于毛囊外周,是维持和再生毛乳头的重要物质基础,是毛囊再生的必要条件。近年研究表明,毛囊真皮鞘细胞不但参与皮肤创伤修复,而且具有成体干细胞特性,有望为皮肤创伤愈合研究和组织工程学研究提供新的思路。本文就毛囊真皮鞘细胞生物学特性研究进展作一综述。     

C57BL/6小鼠皮肤毛囊发育的实验研究

目的探讨胎鼠,乳鼠和成鼠毛囊发育的规律。方法石蜡和冰冻超薄切片,采用HE染色,AP活性染色,油红O染色,凋亡细胞鉴定等方法观察不同时期C57BL/6小鼠毛囊的发育情况。结果胚胎发育第15.5d(E15.5)开始出现毛囊,至E18.5胎鼠背部皮肤逐渐增厚,毛囊逐渐增多。乳鼠出生第1d毛囊大部分处于第4阶段之前,毛囊数量继续增加,至出生第4d皮肤基底层未见新生的毛囊,此时毛囊数量维持不变,出生第9d毛囊达到第8阶段。成鼠脱毛后第9d约有95%的毛囊进入生长Ⅳ期,第17d约有63.3%的毛囊进入退化期,第22d约有85%的毛囊处于退化期。结论小鼠毛囊的早期发育起始于E15.5,从E17.5到出生后3d毛囊数量呈快速增加趋势,因此,这一时期可以用于探讨毛囊再生机制等相关研究。     

人去表皮真皮细胞活性及组织结构特征(英文)

背景:研究证实,去表皮的真皮可以作为真皮替代物,在其上接种角质形成细胞后形成表皮结构。但有关真皮替代物细胞生物活性、组织结构特点及基底膜成分分析的研究报道较少。目的:观察人去表皮真皮细胞活性及组织结构特征。方法:将健康成人皮瓣用56℃PBS溶液处理以去除表皮,用液氮连续冻融处理去除真皮中细胞成分,获得去表皮真皮。以组织块培养法观察去表皮真皮细胞活性。以苏木精染色检测去表皮真皮细胞核,以波形蛋白免疫组化检测去表皮真皮成纤维细胞成分。以PAS染色及Ⅳ型胶原免疫组化检测基底膜及其成分。以VG染色检测去表皮真皮胶原纤维,Weigert染色检测弹力纤维,VG与Weigert双染色检测胶原纤维及弹力纤维,透射及扫描电镜观察去表皮真皮超微结构。结果与结论:用组织块培养方法培养的去表皮真皮2周无细胞生长。苏木精-伊红染色显示去表皮真皮中无细胞核、波形蛋白免疫组化显示去表皮真皮中无波形蛋白表达。VG染色显示去表皮真皮胶原纤维染成玫瑰红色,Weigert染色显示去表皮真皮弹力纤维染成紫黑色,双染色进一步显示胶原纤维与弹力纤维均匀排列。去表皮真皮表面及附属器残留部位PAS反应强阳性,Ⅳ型胶原表达明显。透射及扫描电镜下观察到去表皮真皮中胶原﹑弹力纤维交错排列,间有孔隙,相互交织成网。去表皮真皮无活细胞成分,真皮基质表面及附属器管腔壁仍保留糖原﹑Ⅳ型胶原等基底膜成分,真皮基质中富含胶原及弹力纤维,是一种类似在体真皮的三维胶原基质。     

裸鼠皮下种植性肝癌模型的建立

背景：目前采用Huh7肝癌细胞在BALB/c裸小鼠皮下种植性成瘤的报道较多,但对其成瘤后稳定性的研究较少。 目的：建立稳定的皮下种植性裸鼠肝癌模型。 方法：取1.5×10⁶个对数期细胞Huh7肝癌细胞,种植于裸鼠皮下。成瘤后从体质量、大体形态,肿瘤生长情况,反转录-聚合酶链式反应,苏木精-伊红染色及免疫组织化学多方面进行稳定性及病理学特征鉴定。 结果与结论：肿瘤形成的潜伏期约12 d,肿瘤成功率为92.8%。种植肿瘤组小鼠体质量较正常对照小鼠明显减轻,肿瘤生长迅速,甲胎蛋白基因及蛋白强阳性表达,细胞分裂明显。表明成功建立了稳定的裸鼠皮下种植性肝癌模型。     

β-catenin与小鼠毛囊衰老性变化相关

 摘要：目的探讨β-catenin与毛囊衰老性变化的关系。方法 取老龄与年轻小鼠处于毛囊周期各阶段的皮肤,RT-PCR和Western blot检测β-catenin在mRNA和蛋白水平的表达; IF检测比较β-catenin蛋白表达在毛囊中的组织学分布。结果 老年鼠背皮的β-catenin表达相较处于同一毛囊周期阶段的年轻鼠皮肤在mRNA水平和蛋白质水平均有上调,出生后34个月的小鼠生长期皮肤中β-catenin蛋白的表达为0.9024±0.0167,显著高于出生后35天的0.8012±0.0184。 出生后34个月的小鼠静止期皮肤中β-catenin蛋白表达为0.6348±0.0241,显著高于出生后23天的0.6348±0.0241（P＜0.05）。IF检测显示β-catenin的表达集中在外根鞘和Bulge细胞,也可以观察到β-catenin的入核现象。结论β-catenin表达量上调,周期节律不明显,表达部位不同于年轻鼠可能是衰老相关性白发产生的原因之一。     

低频电磁场影响毛囊生长及KGF表达的实验研究

目的　观察低频电磁场（Low frequency electromagnetic field, LFEMF）对毛囊生长期中再生毛囊的形态学及该过程中角质化细胞生长因子（Keratinocyte growth factor，KGF）表达的影响。 方法　选用雌性C57BL/6成年鼠制作毛囊生长期模型，随机分为对照组和LFEMF组。LFEMF组采用50 Hz、5 mT磁场，30 min/d，连续作用16 d。取两组小鼠脱毛处的全层皮肤，HE染色法观察毛囊生长期中毛囊形态学的改变，荧光定量PCR法和Western-blot检测KGF表达情况。  结果　HE染色显示：3 d时，对照组中未见球状基质包绕毛乳头， LFEMF组球状基质部分包绕毛乳头，毛乳头上部有黑色素形成；9 d、16 d时，LFEMF组中毛囊的长度显著增加（P < 0.05）。荧光定量PCR及Western-blot检测结果表明LFEMF组较对照组的KGF基因转录水平及蛋白水平均上调。  结论　LFEMF能促进毛囊的生长，其机制可能与KGF的分泌增加有关。     

小鼠下颌下腺发育中转化生长因子β受体的表达

背景：小鼠的下颌下腺是研究唾液腺的发育的良好模型,转化生长因子β是器官发育和疾病中重要的生长因子,但是在下颌下腺中转化生长因子β受体的表达以及作用机制至今并不明确。 目的：观察胚胎小鼠下颌下腺发育过程中转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1/2的表达,揭示转化生长因子β在小鼠涎腺发育中的作用。 方法：取C57BL/6J小鼠胚胎期第14.5天的标本,使用转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1/2抗体,对小鼠的下颌下腺进行免疫组化染色。取新生小鼠标本,大体观察下颌下腺,并且使用苏木精-伊红染色观察其形态。 结果与结论：①小鼠出生时,下颌下腺位于下颌骨下方;苏木精-伊红染色发现小鼠下颌下腺的腺泡、导管和闰管细胞也已经分化完成。②在胚胎期第14.5天,转化生长因子βⅠ型和Ⅱ型受体在腺泡上皮和导管上皮内高表达,而腺体上皮细胞外的间充质没有表达。③p-ERK1/2主要也是表达在下颌下腺的上皮细胞中,与转化生长因子βⅠ型受体和Ⅱ型受体在下颌下腺中的表达基本一致。说明在小鼠下颌下腺的发育过程中,转化生长因子β蛋白可能通过与上皮细胞表面的受体结合,激活ERK信号通路来调节涎腺腺泡和导管的发育。     

Bone morphogenetic protein signaling regulates postnatal hair follicle differentiation and cycling

Hair follicle morphogenesis and cycling were examined in transgenic mice that overexpress the bone morphogenetic protein (BMP) inhibitor Noggin under the control of the neuron-specific enolase promoter. The Noggin transgene was misexpressed in the proximal portion of the hair follicle, primarily the matrix cells, apart from the usual expression in neurons. Transgene expression appeared only after induction of both the primary (tylotrich) and secondary (nontylotrich) pelage hair follicles had already occurred, thus allowing examination of the role of BMP signaling in follicles that had been induced normally in the presence of BMPs. The overexpression of Noggin in these animals resulted in a dramatic loss of hair postnatally. There was an apparently normal, but shortened period of postnatal hair follicle morphogenesis, followed by premature initiation of hair follicle cycling via entry into the first catagen transformation. This resulted in a complete loss of hair shafts from the nontylotrich hair follicles in these mice while the tylotrich hair follicles were normal. The onset of anagen of the first postnatal hair follicle cycle was also accelerated in the transgenic mice. Our results show that BMP signaling is specifically required for proper proliferation and differentiation during late morphogenesis of nontylotrich hair follicles and that inhibition of this signaling pathway may be one of the triggers for the onset of catagen when the follicles are in anagen and the onset of anagen when the follicles are in telogen. Ectopic sebocyte differentiation was another hallmark of the phenotype of these transgenic mice suggesting that BMP signaling may be an important determinant of lineage selection by common progenitor cells in the skin. BMPs likely promote a hair follicle-type differentiation pathway of keratinocytes while suppressing the sebaceous differentiation pathway of skin epithelium.     

Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop

During hair follicle morphogenesis, dermal papillae (DPs) function as mesenchymal signaling centers that cross-talk with overlying epithelium to regulate morphogenesis. While the DP regulates hair follicle formation, relatively little is known about the molecular basis of DP formation. The morphogen Sonic hedgehog (Shh) is known for regulating hair follicle epithelial growth, with excessive signaling resulting in basal cell carcinomas. Here, we investigate how dermal-specific Shh signaling contributes to DP formation and hair growth. Using a Cre-lox genetic model and RNAi in hair follicle reconstitution assays, we demonstrate that dermal Smoothened (Smo) loss of function results in the loss of the DP precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype reminiscent of Shh(-/-) skin. Surprisingly, dermal Smo does not regulate cell survival or epithelial proliferation. Rather, molecular screening and immunostaining studies reveal that dermal Shh signaling controls the expression of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral system, we show that overexpression of the Shh-dependent gene Noggin, but not Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle phenotype by increasing the expression of epithelial Shh. Our findings suggest that dermal Shh signaling regulates specific DP signatures to maintain DP maturation while maintaining a reciprocal Shh-Noggin signaling loop to drive hair follicle morphogenesis.     

Bone morphogenetic protein signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion

Epithelial stem cells (EP-SCs) located in the bulge region of a hair follicle (HF) have the potential to give rise to hair follicle stem/progenitor cells that migrate down to regenerate HFs. Bone morphogenetic protein (BMP) signaling has been shown to regulate the HF cycle by inhibiting anagen induction. Here we show that active BMP signaling functions to prevent EP-SC activation and expansion. Dynamic expression of Noggin, a BMP antagonist, releases EP-SCs from BMP-mediated restriction, leading to EP-SC activation and initiation of the anagen phase. Experimentally induced conditional inactivation of the BMP type IA receptor (Bmpr1a) in EP-SCs leads to overproduction of HF stem/progenitor cells and the eventual formation of matricomas. This genetic manipulation of the BMP signaling pathway also reveals unexpected activation of beta-catenin, a major mediator of Wnt signaling. We propose that BMP activity controls the HF cycle by antagonizing Wnt/beta-catenin activity. This is at least partially achieved by BMP-mediated enhancement of transforming growth factor-beta-regulated epithelial cell-specific phosphatase (PTEN) function. Subsequently, PTEN, through phosphatidyl inositol 3-kinase-Akt, inhibits the activity of beta-catenin, the convergence point of the BMP and Wnt signaling pathways.     

Embryonic development of hair follicle pluripotent stem (hfPS) cells

Our laboratory discovered nestin-expressing hair follicle stem cells and demonstrated their pluripotency. We have shown that nestin-positive and K15-negative multipotent hair follicle stem cells are located above the hair follicle bulge, and we termed these cells hair follicle pluripotent stem (hfPS) cells. We have previously shown that hair follicle stem cells can regenerate peripheral nerve and spinal cord. In the present study, we describe the embryonic development of the hair follicle stem cell area (hfPSCA), which is located above the bulge and below the sebaceous glands in the adult mouse. At embryonic day 16.5 (E16.5) of nestindriven GFP (ND-GFP) transgenic mice, which express nestin in hfPS cells, the ND-GFP hair follicle stem cells are located in mesenchymal condensates. At postnatal day 0 (P0), the ND-GFP-expressing cells are migrating to the upper part of the hair follicle from the dermal papilla. At P3, keratin 15 (K15)-positive cells, derived from ND-GFP dermal papilla cells, are located in the outer-root sheath and basal layer of the epidermis. By P10, the ND-GFP have formed the K15-positive outer-root sheath as well as the ND-GFP hfPSA. These results suggest that ND-GFP hfPS cells in the dermal papilla form nestin-expressing hair follicle stem cells in the first hair cycle. These observations provide new insight into the origins of hfPS cells and the hfPSCA.     

Steady and temporary expressions of smooth muscle actin in hair, vibrissa, arrector pili muscle, and other hair appendages of developing rats

The hair erection muscle, arrector pili, is a kind of smooth muscle located in the mammalian dermis. The immunohistochemical study using an antibody against smooth muscle alpha actin (SMA) showed that the arrector pili muscle develops approximately 1-2 weeks after birth in dorsal and ventral skin, but thereafter they degenerate. The arrector pili muscle was not detected in the mystacial pad during any stage of development, even in the neighboring pelage-type hair follicle. A strong signal of SMA in the skin was located in the dermal sheath as well as in some outer root sheath cells in the hair and vibrissal follicles. Positive areas in the dermal and outer root sheaths were restricted to a lower moiety, particularly areas of similar height, where keratinization of the hair shaft occurs. This rule is valid for both pelage hair follicles and vibrissal follicles. At medium heights of the follicle, SMA staining in the dermal sheath was patchy and distant from the boundary between dermis and epidermis. In contrast to SMA, vimentin was expressed over the entire height of the dermal sheath. Unlike the arrector pili muscle, the expression of SMA in the dermal sheath was observed during fetal, neonatal, and adult stages. The presence of actin-myosin and vimentin fibers in supporting cells is thought to be beneficial for the hair follicle to cope with the movement of the hair shaft, which may be caused by physical contacts with outside materials or by the contraction of internal muscles.     

Immunolocalization of Wnt5a during the hair cycle and its role in hair shaft growth in mice

Previous studies have shown that the Wnt signaling pathway plays an important role in the growth and development of hair follicles. It has been generally accepted that Wnt5a, a non-canonical Wnt gene, inhibits the Wnt/β-catenin signaling pathway. Several reports have addressed its mRNA expression in embryonic and postnatal hair follicles, but its exact role in the growth of hair follicles is currently unknown. In this study, we investigated the immunolocalization of Wnt5a protein in pelages of the dorsal skin and whisker follicles of mice. We found that in the anagen phase, dermal papilla cells showed the highest staining levels of Wnt5a protein, while in the catagen and the telogen phases the staining levels were lower. During the growth stage, Wnt5a protein was prominently located in the matrix and precortex cells in addition to the inner root sheath, outer root sheath and the dermal papilla. As the hair cycle progresses, the immunostaining of Wnt5a was gradually decreased in the catagen phase and was located in the bulge and secondary hair germ in the telogen phase. This Wnt5a immunostaining profile was consistent between dorsal skin pelages and whisker follicles. Furthermore, in an in vitro study using whisker follicle organ culture, we demonstrated that the growth of the hair shaft was significantly inhibited by adenovirus Wnt5a. Our findings suggest that Wnt5a is a dynamic factor in the hair cycle and it is important for the regulation of hair shaft growth.     

Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic protein pathway activity at the dermal-epidermal interface

Epithelial appendages, such as mammary glands and hair, arise as a result of epithelial-mesenchymal interactions. Bone morphogenetic proteins (BMPs) are important for hair follicle morphogenesis and cycling and are known to regulate a wide variety of developmental processes. For example, overexpression of BMPs inhibits hair follicle formation. We hypothesized that the down-regulation of the BMP signaling pathway in the basal epidermis expands regions that are competent to form hair follicles and could alter the fate of the epithelium in the mouse nipple to a hair-covered epidermal phenotype. To test our hypothesis, we used a transgenic mouse model in which keratin 14 (KRT14) promoter-mediated overexpression of Noggin, a BMP antagonist, modulates BMP activity. We observed the conversion of nipple epithelium into pilosebaceous units. During normal mammary gland organogenesis, BMPs are likely used by the nipple epithelium to suppress keratinocyte differentiation, thus preventing the formation of pilosebaceous units. In this report, we characterize the morphology and processes that influence the development of hairs within the nipple of the KRT14-Noggin mouse. We demonstrate that Noggin acts, in part, by reducing the BMP signal in the epithelium. Reduction of the BMP signal in turn leads to a reduction in the levels of parathyroid hormone-related protein. We propose that during evolution of the nipple, the BMP pathway was co-opted to suppress hair follicle formation and create a more functional milk delivery apparatus.     

Dynamic signals for hair follicle development and regeneration

Hair follicles form during embryonic development and, after birth, undergo recurrent cycling of growth, regression, and relative quiescence. As a functional mini-organ, the hair follicle develops in an environment with dynamic and alternating changes of diverse molecular signals. Over the past decades, genetically engineered mouse models have been used to study hair follicle morphogenesis and significant advances have been made toward the identification of key signaling pathways and the regulatory genes involved. In contrast, much less is understood in signals regulating hair follicle regeneration. Like hair follicle development, hair follicle regeneration probably relies on populations of stem cells that undergo a highly coordinated and stepwise program of differentiation to produce the completed structure. Here, we review recent advances in the understanding of the molecular signals underlying hair follicle morphogenesis and regeneration, with a focus on the initiation of the primary hair follicle structure placode. Knowledge about hair follicle morphogenesis may help develop novel therapeutic strategies to enhance cutaneous regeneration and improve wound healing.     

Comparative characterization of hair follicle dermal stem cells and bone marrow mesenchymal stem cells

We compared the growth and differentiation characteristics of hair follicle-derived dermal stem cells with bone marrow mesenchymal stem cells (MSCs). Follicular dermal cells were isolated from whisker hairs of Wistar rats and bone marrow MSCs were isolated from femora of the same animals. The adherent hair follicle dermal cells showed a fibroblastic morphology in serum-containing culture medium, were CD44(+), CD73(+), CD90(+), and CD34(), and had a population doubling time of 27 h. MSCs isolated from the bone marrow showed a similar morphology and population doubling time and expressed the same cell-surface markers. Following exposure to appropriate induction stimuli, both cell populations had the capacity to differentiate into various mesenchymal lineages, such as osteoblasts, adipocytes, chondrocytes, and myocytes and expressed neuroprogenitor cell markers. The rate and extent of differentiation were remarkably similar for both hair follicleand bone marrow-derived cells, whereas interfollicular dermal cells failed to differentiate. We identified telomerase activity in follicle dermal stem cells and marrow MSCs and demonstrated that they were capable of clonal expansion. In ex vivo analyses, we identified the presence of putative dermal stem cells in the dermal sheath and dermal papillae of the hair follicle. Consequently, the hair follicle may represent a suitable, accessible source for MSCs.