scholarly journals Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit Expression

2002 ◽  
Vol 50 (6) ◽  
pp. 751-766 ◽  
Author(s):  
Eva M. J. Peters ◽  
Desmond J. Tobin ◽  
Natasha Botchkareva ◽  
Marcus Maurer ◽  
Ralf Paus
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Stem Cell Factor ◽  
Mouse Skin ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Cell Populations ◽  
Outer Root Sheath ◽  
Hair Bulb ◽  
Root Sheath

Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles.

scholarly journals CCN2 modulates hair follicle cycling in mice

2013 ◽  
Vol 24 (24) ◽  
pp. 3939-3944 ◽  
Author(s):  
Shangxi Liu ◽  
Andrew Leask
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Activity ◽  
Adult Life ◽  
Tissue Growth ◽  
Hair Follicles ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Dermal Papillae

It is critical to understand how stem cell activity is regulated during regeneration. Hair follicles constitute an important model for organ regeneration because, throughout adult life, they undergo cyclical regeneration. Hair follicle stem cells—epithelial cells located in the follicle bulge—are activated by periodic β-catenin activity, which is regulated not only by epithelial-derived Wnt, but also, through as-yet-undefined mechanisms, the surrounding dermal microenvironment. The matricellular protein connective tissue growth factor (CCN2) is secreted into the microenvironment and acts as a multifunctional signaling modifier. In adult skin, CCN2 is largely absent but is unexpectedly restricted to the dermal papillae and outer root sheath. Deletion of CCN2 in dermal papillae and the outer root sheath results in a shortened telogen-phase length and elevated number of hair follicles. Recombinant CCN2 causes decreased β-catenin stability in keratinocytes. In vivo, loss of CCN2 results in elevated numbers of K15-positive epidermal stem cells that possess elevated β-catenin levels and β-catenin–dependent reporter gene expression. These results indicate that CCN2 expression by dermal papillae cells is a physiologically relevant suppressor of hair follicle formation by destabilization of β-catenin and suggest that CCN2 normally acts to maintain stem cell quiescence.

scholarly journals The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 154
Author(s):  
Hanluo Li ◽  
Federica Francesca Masieri ◽  
Marie Schneider ◽  
Alexander Bartella ◽  
Sebastian Gaus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Gene And Protein Expression ◽  
Stem Cell Populations

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells.

scholarly journals Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles

2008 ◽  
Vol 197 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Valerie A Randall ◽  
Tracey J Jenner ◽  
Nigel A Hibberts ◽  
Isabel O De Oliveira ◽  
Tayyebeh Vafaee
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Androgenetic Alopecia ◽  
Hair Colour ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Factor C

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocyte-lineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.

scholarly journals The Glypican-1/HGF/C-Met and Glypican-1/VEGF/VEGFR2 Ternary Complexes Regulate Hair Follicle Angiogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Charlie Colin-Pierre ◽  
Nicolas Berthélémy ◽  
Nicolas Belloy ◽  
Louis Danoux ◽  
Vincent Bardey ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Dermal Papilla ◽  
Human Keratinocytes ◽  
Hair Follicles ◽  
Microvascular Endothelial Cell ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Microvascular Endothelial

The hair renewal involves changes in the morphology of the hair follicle and its micro-vascularization. In alopecia, the hair cycle is accelerated, resulting in the formation of thinner and shorter hair. In addition, alopecia is associated with a decrease in the micro-vascularization of the hair follicles. In this study, the role of glypicans (GPCs) was analyzed in the regulation of the angiogenesis of human dermal microvascular endothelial cells (HDMEC). The analysis of glypican gene expression showed that GPC1 is the major glypican expressed by human keratinocytes of outer root sheath (KORS), human hair follicle dermal papilla cells (HHFDPC) and HDMEC. KORS were demonstrated to secrete VEGF and HGF. The HDMEC pseudotube formation was induced by KORS conditioned media (KORSCM). It was totally abrogated after GPC1 siRNA transfection of HDMEC. Moreover, when cleaved by phospholipase C (PLC), GPC1 promotes the proliferation of HDMEC. Finally, GPC1 was shown to interact directly with VEGFR2 or c-Met to regulate angiogenesis induced by the activation of these receptors. Altogether, these results showed that GPC1 is a key regulator of microvascular endothelial cell angiogenesis induced by VEGF and HGF secreted by KORS. Thus, GPC1 might constitute an interesting target to tackle alopecia in dermatology research.

scholarly journals Exposure to 50 Hz electromagnetic fields enhances hair follicle regrowth in C57BL/6 mice

2019 ◽  
Vol 244 (5) ◽  
pp. 389-394
Author(s):  
Xinping Li ◽  
Xin Wang ◽  
Liming Bai ◽  
Pin Zhao ◽  
Mingsheng Zhang
Keyword(s):  
Stem Cells ◽  
Electromagnetic Field ◽  
Growth Factors ◽  
Hair Follicle ◽  
Electromagnetic Fields ◽  
Hair Follicles ◽  
Control Group ◽  
Outer Root Sheath ◽  
Hair Bulb ◽  
Root Sheath

Many studies have suggested that electromagnetic field activity affects the cellular activity of many types of cells involved in forming hair follicles. However, the bio-effects of electromagnetic fields on hair follicle growth have not been fully elucidated. This present study was designed to determine whether 50 Hz electromagnetic fields increased hair follicle regrowth. In this experiment, C57BL/6 mice were used to present the model of depilation-induced hair follicle cycling, and then those mice were divided at random into the control group and the electromagnetic field group. After electromagnetic field (50 Hz, 5 mT) exposure for 16 days, the skin specimens of the mice were harvested to assess for hair regrowth, and epidermal stem cells proliferation was evaluated by immunofluorescence staining. The expression and location of keratinocyte growth factors were also tested. Our results showed that, compared to the control, the hair club formed faster on the 3rd day, and most of the hair shafts erupted earlier from the pore in the epidermis on the 9th day after depilation, and the hairs length was significantly longer on the 16th day within the electromagnetic field group. After electromagnetic field treatment, there were more Ki67+ cells in the outer root sheath and hair bulb where it co-localized with K15+ cells compared to the control. Keratinocyte growth factors were expressed in the inner root sheath in both groups, and the electromagnetic field group showed more expression of keratinocyte growth factors. Our data suggested that the hair-growth-promoting effect of the 50 Hz electromagnetic field was observed in depilation-induced hair follicles cycling, which was associated with 50 Hz electromagnetic field enhancing K15+ stem cells proliferation and increased keratinocyte growth factor expression. Impact statement In this study, our experiments confirmed that 50 Hz EMF affected hair follicle regrowth, and 50 Hz EMF enhanced K15+ stem cells proliferation in the hair bulb and follicular outer root sheath of hair follicles. Those results indicated that 50 Hz EMF may be beneficial for functional healing of hair loss.

scholarly journals NG2 Proteoglycan Expression in Mouse Skin: Altered Postnatal Skin Development in the NG2 Null Mouse

2007 ◽  
Vol 56 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Kuniko Kadoya ◽  
Jun-ichi Fukushi ◽  
Yoshihiro Matsumoto ◽  
Yu Yamaguchi ◽  
William B. Stallcup
Keyword(s):  
Stem Cell ◽  
Mouse Skin ◽  
Hair Follicles ◽  
Stem Cell Population ◽  
Null Mouse ◽  
Outer Root Sheath ◽  
Skin Development ◽  
Bulge Region ◽  
Ng2 Proteoglycan ◽  
Stem Cell Populations

In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis, the dermis, the outer root sheath of hair follicles, and the basal keratinocyte layer of the epidermis. With further development, NG2 is most prominently expressed by stem cells in the hair follicle bulge region, as also observed in adult human skin. During telogen and anagen phases of the adult hair cycle, NG2 is also found in stem cell populations that reside in dermal papillae and the outer root sheaths of hair follicles. Ablation of NG2 produces alterations in both the epidermis and subcutis layers of neonatal skin. Compared with wild type, the NG2 null epidermis does not achieve its full thickness due to reduced proliferation of basal keratinocytes that serve as the stem cell population in this layer. Thickening of the subcutis is also delayed in NG2 null skin due to deficiencies in the adipocyte population.

Communication compartments in hair follicles and their implication in differentiative control

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 389-393 ◽  
Author(s):  
E. Kam ◽  
M.B. Hodgins
Keyword(s):  
Lucifer Yellow ◽  
Early Stage ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Dye ◽  
Hair Bulb ◽  
Ultrastructural Studies ◽  
Junctional Communication ◽  
Root Sheath ◽  
Inner Root Sheath

Observations on hair follicles presented in this paper show that boundaries to junctional communication are formed between groups of cells following different pathways of differentiation. The patterns of junctional communication in the bulbs of rat vibrissa follicles and human hair follicles were studied by microinjection of the fluorescent tracer dye Lucifer Yellow CH. Dye spread was extensive between undifferentiated cells of the hair bulb matrix but communication boundaries were found between groups of morphologically distinct cells. For example, boundaries to dye spread were observed between undifferentiated matrix cells and cells in the early stage of differentiation into the inner root sheath, between Huxley's and Henle's layers in the early inner root sheath and between cells of the cuticle and cortex of the hair. Dye did not spread between epithelial cells of the hair bulb and mesenchymal cells of the connective tissue sheath or dermal papilla. The patterns of dye spread became more complex (increased boundary formation and subcompartmentation) as differentiation progressed in higher regions of the hair bulb. The observed communication can be related to previous ultrastructural studies by others on the distribution of gap junctions in the wool follicle. These results show that junctional communication, with its consequent intercellular spread of small ions and molecules, is associated with uniformity of expression and behaviour within cell populations and that interruption of communication through the formation of boundaries and communication compartments is temporally and spatially related to the production of subpopulations of cells committed to the expression of different phenotypes.

scholarly journals Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

2020 ◽  
Vol 21 (16) ◽  
pp. 5672
Author(s):  
Kyung-Eun Ku ◽  
Nahyun Choi ◽  
Jong-Hyuk Sung
Keyword(s):  
Hair Growth ◽  
Expression Patterns ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

scholarly journals Integrin-linked kinase is required for epidermal and hair follicle morphogenesis

2007 ◽  
Vol 177 (3) ◽  
pp. 501-513 ◽  
Author(s):  
Katrin Lorenz ◽  
Carsten Grashoff ◽  
Robert Torka ◽  
Takao Sakai ◽  
Lutz Langbein ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Leading Edge ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Membrane Dynamics ◽  
Epidermal Keratinocytes ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Integrin Linked Kinase

Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal–dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers. The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.

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