White hair can be saved! New research reveals the causes of hair whitening and finds intervention targets

The following is the White hair can be saved! New research reveals the causes of hair whitening and finds intervention targets recommended by recordtrend.com. And this article belongs to the classification: Life data.

Hair whitening is often regarded as a natural phenomenon of human aging. Middle-aged and elderly people often dye their hair to make themselves look younger. Hair color and health are closely related to hair follicles. Hair follicle is the skin organ responsible for the growth of hair. It is also the only mammalian organ that circulates periodically throughout its life. It is distributed on the skin of the whole body except the palms, feet and lips.

In addition, hair follicles can help the epidermis to maintain the body from the damage of the external environment, and play an important role in physiological tissue renewal and trauma repair. Because the working mechanism of human hair follicles in disease and health is not clear, the common phenomena of hair loss and hair graying are generally not well controlled, and even some “folk prescriptions” that treat symptoms but not root causes may lead to other health problems.

Hair whitening is usually a gradual process from middle age. Nishimura, e. K. et al. Have found that hair graying related to aging is related to the depletion of melanocytes and melanocyte stem cells (MESC). This depletion process may be affected by skin microenvironment factors, such as oxidative stress and neuroendocrine signals.

Hair, like nails, is mostly composed of cutin. White hair is also different from colored hair in growth rate and biophysical properties, indicating that their hair follicle epithelial lineage has changed. Tanimura, S. et al. And Lu, Z. et al. Found through mouse studies that epithelial stem cells in hair follicles provide functional niches for melanocyte stem cells and guide their differentiation.

To study hair whitening, we should start with hair follicles. So what is the hair follicle cell lineage from the microscopic perspective? On May 24, 2022, Zhang Liang, a research team from Shanghai Institute of nutrition and health, Chinese Academy of Sciences, and others published a research paper “single cell transcriptomics reveals the lineage track of human scalp hair follicles and reveals the mechanism of hair graying” on cell discovery.

Through single-cell transcriptome sequencing, it was found that the early stage of human hair whitening was related to the specific depletion of stromal hair progenitor cells, not hair follicle stem cells. The depletion of hair progenitor cells is accompanied by the activation of p53 pathway. The addition of p53 inhibitors can improve the hair whitening of mice. This study has opened up a promising way to improve the condition of hair whitening.

After obtaining the informed consent of healthy individuals, the researchers collected their abandoned plastic surgery specimens. After these human scalp samples were processed, the researchers used tweezers to remove the hair follicles one by one. Subsequently, the researchers sequenced the single cell transcriptome of hair follicle cell suspension.

Note: single cell transcriptome sequencing reveals the cell type composition of human scalp hair follicles

After obtaining the sequencing data, the researchers roughly described the characteristics of 12 clusters of cells according to the expression of known lineage markers. We also used monocle3 to do pseudo time analysis to study the difference trajectories among 10 hair follicle epithelial cell clusters. From the immunofluorescence staining diagram, we can see the spatial distribution of different hair follicle cell groups, in which the fluorescence labeled krt15 and CD200 is enriched in the middle and upper part of the hair follicle.

By further clustering SC1 and SC2 cell populations in human scalp transcriptome data, researchers found that human scalp hair follicles showed different molecular characteristics from mice. After further grouping of proliferating cells, it was found that human stromal transient amplification cells (TAC) contained heterogeneous cell populations with obvious differentiation trend. Mxta subpopulations follow the characteristic topologies of different lineages and branch from the central progenitor cell group (M2).

Note: scenario analysis reveals the transcriptional regulatory network in human scalp hair follicles

In order to deeply understand the transcriptional regulatory networks in human scalp hair follicles, researchers used scene to identify the significantly enriched gene regulatory networks (regulators) corresponding to specific transcription factors in each cell group, and identified 56 important transcriptional regulators. The known regulators of Msx2 and LEF1, the key transcription factors of hair follicle matrix, are enriched in the matrix group as expected.

The regulators of Jun and Fos (two AP-1 family transcription factors) are enriched in human hair follicle stem cells. These two families have not been involved in the regulation of mouse adult hair follicle stem cells. These data suggest that the transcriptional regulation of human hair follicle stem cells may be significantly different from that of mice. GSEA analysis showed that in most cell populations, the changes of f62w-vs-f62b (old) gene expression were highly consistent with those of f31w-vs-f31b (young), indicating that hair graying in young and old individuals was regulated by a common transcription mechanism.

Compared with black human scalp hair follicles, the number of immune cells in white human scalp hair follicles increased significantly. Depletion of stromal transient expansion cells is a major hair follicle change associated with hair graying. P53 pathway target p2159 and DNA damage marker histone γ H2ax60 also increased significantly in white human scalp hair follicle cell matrix, which supports the view that p53 pathway is activated in gray human scalp hair follicle matrix.

Note: drug inhibition of p53 pathway can improve the hair graying of mice induced by ionizing radiation

Finally, the researchers took the p53 inhibitor pifithrin alpha (PFT α） 63 or solvent control (SOL) was administered locally to local ionizing radiation (LIR) mice at a dose of 2 μ G/cm2, once every 3 days, 5 times in total. PFT α Treatment significantly reduced the hair graying phenotype in the exposed skin area, but did not cause significant changes in the untreated skin area of the same mice.

In this study, the researchers excluded the interference of inter follicular epidermis, dermis and various other tissues, only studied the cell composition of hair follicles, explored the regulatory factors of different cell groups, and found the pathways related to hair whitening. And confirmed the inhibitor PFT of this pathway α In mice, it is effective in graying hair, which brings enlightenment to the treatment of white hair.

Reference source:

1.Nishimura, E. K., Granter, S. R. & Fisher, D. E. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307, 720–724 (2005).

2.Tanimura, S. et al. Hair follicle stem cells provide a functional niche for melanocyte stem cells. Cell Stem Cell 8, 177–187 (2011).

3.Lu, Z. et al. Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells. Elife 9

4.Wu, Sijie, Yao Yu, Caiyue Liu, Xia Zhang, Peiying Zhu, You Peng, Xinyu Yan et al. “Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying.” Cell Discovery 8, no. 1 (2022): 1-20.

By rattisha

Editor | little ear

From: biological Valley

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