scholarly journals Mouse notch: expression in hair follicles correlates with cell fate determination.

1993 ◽  
Vol 121 (3) ◽  
pp. 631-641 ◽  
Author(s):  
R Kopan ◽  
H Weintraub
Keyword(s):  
Hair Follicle ◽  
Cell Fate ◽  
Dermal Papilla ◽  
Cell Types ◽  
Cell Interaction ◽  
Hair Follicles ◽  
Skin Development ◽  
High Level ◽  
Cell Cell

Many vertebrate tissues, including skin, are known to develop as a consequence of epithelial-mesenchymal interactions. Much less is known about the role of cell-cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle. mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle.

Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2421-2432 ◽  
Author(s):  
M.H. Lin ◽  
C. Leimeister ◽  
M. Gessler ◽  
R. Kopan
Keyword(s):  
Transgenic Mice ◽  
Hair Follicle ◽  
Active Form ◽  
Notch Pathway ◽  
Dermal Papilla ◽  
Cell Types ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Hair Cortex

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.

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 CULTURED HAIR FOLLICLE CELLS FOR THE TREATMENT OF VITILIGO

2018 ◽  
Vol 11 (15) ◽  
pp. 94
Author(s):  
Piyatida Sutnut ◽  
Saroj Suvanasuthi ◽  
Kwanchanok Viravaidya-pasuwat
Keyword(s):  
Human Serum ◽  
Hair Follicle ◽  
Cell Attachment ◽  
Fetal Bovine Serum ◽  
Dermal Papilla ◽  
Cell Types ◽  
Hair Follicles ◽  
Follicle Cells ◽  
Fetal Bovine ◽  
Different Cell Types

Objective: The objective of this study was to develop a method to isolate cells from hair follicles and cultured them in a hydrogel.Methods: Different cell types obtained from hair follicles were investigated and mixed with three formulations of Lutrol® F-127-based hydrogels. The percentages of the cell attachment and viability were observed within 48 h.Results: The results showed that three cell types, including keratinocyte, dermal papilla, and melanocyte cells, were obtained, as shown by the expression of their corresponding genes. All formulations of the hydrogels supported cell attachment and viability. Interestingly, more than 60% cell attachment and viability were found in lutrol hydrogels supplemented with either fetal bovine serum (FBS) or heat-activated human serum.Conclusion: Higher cell attachment and viability were observed when the hair follicle cells were cultured in the hydrogel with FBS than the hydrogel with human serum. However, the lutrol gel formulation with human serum was more appropriate to be used in the future clinical study, as this formulation contained no animal-derived component.

scholarly journals 10×Genomics Single-cell Sequencing Reveals Differential Cell Types in Skin Tissues of Liaoning Cashmere Goats and Key Genes Related Potentially to the Fineness of Cashmere Fiber

2020 ◽  
Author(s):  
Yuanyuan Zheng ◽  
Yanru Wang ◽  
Taiyu Hui ◽  
Yanan Xu ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Single Cell ◽  
Hair Follicle ◽  
Computational Models ◽  
Marker Gene ◽  
Dermal Papilla ◽  
Cell Types ◽  
Dermal Papilla Cells ◽  
Skin Development ◽  
Timeline Analysis ◽  
Cashmere Goats

Abstract Cashmere fineness is one of the important factors determining cashmere quality, however, our understanding about the cells that make up the cashmere fineness is limited. Here, we used single-cell RNA sequencing (scRNA-seq) and computational models to identify 13 skin cell types in Liaoning Cashmere Goats. We also analyzed the molecular changes by Pseudo-Timeline Analysis in the development process and revealed the maturation process in gene expression profile in Liaoning Cashmere Goats. Weighted gene co-expression network analysis (WGCNA) explored hub genes in cell clusters related to cashmere formation. Secondary hair follicle dermal papilla cells (SDPCs) play an important role in the growth and density of cashmere. ACTA2, a marker gene of SDPCs, was selected for immunofluorescence (IF) and western blot (WB) verification. It was proved that it was mainly expressed in SDPCs, and WB results showed different expression levels. COL1A1 is a high expression gene in SDPCs, which was verified by IF and WB. Then select the function gene CXCL8 of SDPCs to verify, and prove the differential expression in the coarse type and the fine type of Liaoning Cashmere Goats. Therefore, COL1A1 may involve in regulated skin development and CXCL8 gene may regulate cashmere fineness. These genes may be involved in regulating the fineness of cashmere in goat secondary hair follicle dermal papilla cells, our research will provide new insights into the mechanism of cashmere growth and cashmere fineness regulation by cells.

scholarly journals Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle

2021 ◽  
Author(s):  
Megan A. Palmer ◽  
Eleanor Smart ◽  
Iain S. Haslam
Keyword(s):  
Hair Follicle ◽  
Human Hair ◽  
Vital Role ◽  
Transport Proteins ◽  
Hair Follicles ◽  
Regulatory Control ◽  
Cholesterol Transport ◽  
Hair Cycle ◽  
Human Hair Follicle

AbstractCholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.

scholarly journals SUMOylation Negatively Regulates Angiogenesis by Targeting Endothelial NOTCH Signaling

2017 ◽  
Vol 121 (6) ◽  
pp. 636-649 ◽  
Author(s):  
Xiaolong Zhu ◽  
Sha Ding ◽  
Cong Qiu ◽  
Yanna Shi ◽  
Lin Song ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Developmental Disorders ◽  
Interaction Mechanism ◽  
Growth Factor Receptor ◽  
Vascular Diseases ◽  
Cell Interaction ◽  
Protein Signaling

Rationale: The highly conserved NOTCH (neurogenic locus notch homolog protein) signaling pathway functions as a key cell–cell interaction mechanism controlling cell fate and tissue patterning, whereas its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders. Objective: The aim of this study was to investigate the role of SUMOylation in endothelial NOTCH signaling and angiogenesis. Methods and Results: Endothelial SENP1 (sentrin-specific protease 1) deletion, in newly generated endothelial SENP1 (the major protease of the SUMO system)–deficient mice, significantly delayed retinal vascularization by maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and immunoprecipitation analyses and dual-luciferase assays of natural and SUMO-conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized it for translocation to the nucleus where it functions as a cotranscriptional factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn suppressed VEGF (vascular endothelial growth factor) receptor signaling and angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro angiogenesis assays. Conclusions: These results establish reversible NOTCH1 SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic signaling; SENP1 acts as a critical intrinsic mediator of this process. These findings may apply to NOTCH-regulated biological events in nonvascular tissues and provide a novel therapeutic strategy for vascular diseases and tumors.

Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro

1991 ◽  
Vol 99 (3) ◽  
pp. 627-636 ◽  
Author(s):  
C.A. Jahoda ◽  
A.J. Reynolds ◽  
C. Chaponnier ◽  
J.C. Forester ◽  
G. Gabbiani
Keyword(s):  
Smooth Muscle ◽  
Hair Follicle ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Dermal Papilla Cells ◽  
Smooth Muscle Alpha Actin ◽  
Actin Expression ◽  
Alpha Actin ◽  
Sheath Cells

We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

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