Nuclear localization of Meis1 in dermal papilla promotes hair matrix cell proliferation in the anagen phase of hair cycle

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

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De Novo Production of Dermal Papilla Cells during the Anagen Phase of the Hair Cycle

Journal of Investigative Dermatology ◽

10.1038/jid.2010.176 ◽

2010 ◽

Vol 130 (11) ◽

pp. 2664-2666 ◽

Cited By ~ 26

Author(s):

Woo Y. Chi ◽

David Enshell-Seijffers ◽

Bruce A. Morgan

Keyword(s):

De Novo ◽

Dermal Papilla ◽

Hair Cycle ◽

Dermal Papilla Cells ◽

Anagen Phase

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Activin B Stimulates Mouse Vibrissae Growth and Regulates Cell Proliferation and Cell Cycle Progression of Hair Matrix Cells through ERK Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms20040853 ◽

2019 ◽

Vol 20 (4) ◽

pp. 853

Author(s):

Pei Tang ◽

Xueer Wang ◽

Min Zhang ◽

Simin Huang ◽

Chuxi Lin ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Cycle Progression ◽

Erk Signaling ◽

Follicle Growth ◽

Cycle Progression ◽

Matrix Cell ◽

Hair Matrix

Activins and their receptors play important roles in the control of hair follicle morphogenesis, but their role in vibrissae follicle growth remains unclear. To investigate the effect of Activin B on vibrissae follicles, the anagen induction assay and an in vitro vibrissae culture system were constructed. Hematoxylin and eosin staining were performed to determine the hair cycle stages. The 5-ethynyl-2′-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays were used to examine the cell proliferation. Flow cytometry was used to detect the cell cycle phase. Inhibitors and Western blot analysis were used to investigate the signaling pathway induced by Activin B. As a result, we found that the vibrissae follicle growth was accelerated by 10 ng/mL Activin B in the anagen induction assay and in an organ culture model. 10 ng/mL Activin B promoted hair matrix cell proliferation in vivo and in vitro. Moreover, Activin B modulates hair matrix cell growth through the ERK–Elk1 signaling pathway, and Activin B accelerates hair matrix cell transition from the G1/G0 phase to the S phase through the ERK–Cyclin D1 signaling pathway. Taken together, these results demonstrated that Activin B may promote mouse vibrissae growth by stimulating hair matrix cell proliferation and cell cycle progression through ERK signaling.

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miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.593638 ◽

2020 ◽

Vol 8 ◽

Author(s):

Yuxin Chen ◽

Junfei Huang ◽

Zhen Liu ◽

Ruosi Chen ◽

Danlan Fu ◽

...

Keyword(s):

Cell Proliferation ◽

Extracellular Vesicles ◽

Hair Growth ◽

Dermal Papilla ◽

Luciferase Reporter ◽

Outer Root Sheath ◽

Dermal Papilla Cells ◽

Root Sheath ◽

Hair Matrix ◽

Low Passage

The application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs regulate HF growth mainly through their unique paracrine properties, raising the possibility of therapies based on extracellular vesicles (EVs). In this study, we explored the effects of EVs from high- and low-passage human scalp follicle dermal papilla cells (DP-EVs) on activation of hair growth, and investigated the underlying mechanism. DP-EVs were isolated by ultracentrifugation and cultured with human scalp follicles, hair matrix cells (MxCs), and outer root sheath cells (ORSCs), and we found low-passage DP-EVs accelerated HF elongation and cell proliferation activation. High-throughput miRNA sequencing and bioinformatics analysis identified 100 miRNAs that were differentially expressed between low- (P3) and high- (P8) passage DP-EVs. GO and KEGG pathway analysis of 1803 overlapping target genes revealed significant enrichment in the BMP/TGF-β signaling pathways. BMP2 was identified as a hub of the overlapping genes. miR-140-5p, which was highly enriched in low-passage DP-EVs, was identified as a potential regulator of BMP2. Direct repression of BMP2 by miR-140-5p was confirmed by dual-luciferase reporter assay. Moreover, overexpression and inhibition of miR-140-5p in DP-EVs suppressed and increased expression of BMP signaling components, respectively, indicating that this miRNA plays a critical role in hair growth and cell proliferation. DP-EVs transport miR-140-5p from DPCs to epithelial cells, where it downregulates BMP2. Therefore, DPC-derived vesicular miR-140-5p represents a therapeutic target for alopecia.

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Faculty Opinions recommendation of De novo production of dermal papilla cells during the anagen phase of the hair cycle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7281957.7530055 ◽

2010 ◽

Author(s):

Bruno Bernard

Keyword(s):

De Novo ◽

Dermal Papilla ◽

Hair Cycle ◽

Dermal Papilla Cells ◽

Anagen Phase

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The PD-1/PD-L1 pathway in murine hair cycle transition: a potential anagen phase regulator

Archives of Dermatological Research ◽

10.1007/s00403-020-02169-9 ◽

2021 ◽

Author(s):

Lijuan Zhou ◽

Liang Wen ◽

Youyu Sheng ◽

Jinghao Lu ◽

Ruiming Hu ◽

...

Keyword(s):

Hair Cycle ◽

Anagen Phase

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Aqueous Extract of Red Deer Antler Promotes Hair Growth by Regulating the Hair Cycle and Cell Proliferation in Hair Follicles

The Scientific World JOURNAL ◽

10.1155/2014/878162 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Jing-jie Li ◽

Zheng Li ◽

Li-juan Gu ◽

Yun-bo Wang ◽

Mi-ra Lee ◽

...

Keyword(s):

Cell Proliferation ◽

Aqueous Extract ◽

Hair Growth ◽

Red Deer ◽

Growth Parameters ◽

Hair Follicles ◽

Control Group ◽

Deer Antler ◽

Vehicle Control Group ◽

Anagen Phase

Deer antlers are the only mammalian appendage capable of regeneration. We aimed to investigate the effect of red deer antler extract in regulating hair growth, using a mouse model. The backs of male mice were shaved at eight weeks of age. Crude aqueous extracts of deer antler were prepared at either 4°C or 100°C and injected subcutaneously to two separate groups of mice (n=9) at 1 mL/day for 10 consecutive days, with water as a vehicle control group. The mice skin quantitative hair growth parameters were measured and 5-bromo-2-deoxyuridine was used to identify label-retaining cells. We found that, in both the 4°C and the 100°C deer antler aqueous extract-injection groups, the anagen phase was extended, while the number of BrdU-incorporated cells was dramatically increased. These results indicate that deer antler aqueous extract promotes hair growth by extending the anagen phase and regulating cell proliferation in the hair follicle region.

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Feature-Based Molecular Networks Identification of Bioactive Metabolites from Three Plants of the Polynesian Cosmetopoeia Targeting the Dermal Papilla Cells of the Hair Cycle

Molecules ◽

10.3390/molecules27010105 ◽

2021 ◽

Vol 27 (1) ◽

pp. 105

Author(s):

Kristelle Hughes ◽

Raimana Ho ◽

Stéphane Greff ◽

Gaëtan Herbette ◽

Edith Filaire ◽

...

Keyword(s):

Hair Follicle ◽

Pearson Correlation ◽

Dermal Papilla ◽

French Polynesia ◽

Bioactive Molecules ◽

Molecular Networks ◽

Bioactive Metabolites ◽

Hair Cycle ◽

Bidens Pilosa ◽

Dermal Papilla Cells

The term cosmetopoeia refers to the use of plants in folks’ cosmetics. The aerial parts of Bidens pilosa L., the leaves of Calophyllum inophyllum L. and the fruits of Fagraea berteroana A.Gray ex Benth are traditionally used in French Polynesia for hair and skin care. During the hair cycle, dermal papilla cells and their interaction with epithelial cells are essential to promote hair follicle elongation. The aim of our investigations was the identification of metabolites from these three plants and chemical families responsible for their hair growth activity. A bioactivity-based molecular network was produced by mapping the correlation between features obtained from LC-MS/MS data and dermal papilla cell proliferation, using the Pearson correlation coefficient. The analyses pointed out glycosylated flavonols and phenolic acids from B. pilosa and C. inophyllum, along with C-flavonoids, iridoids and secoiridoids from F. berteroana, as potential bioactive molecules involved in the proliferation of hair follicle dermal papilla cells. Our results highlight the metabolites of the plant species potentially involved in the induction of hair follicle growth and support the traditional uses of these plants in hair care.

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