June 25, 2024

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SASP of senescent cells may help solve the problem of hair loss that makes people bald

SASP of senescent cells may help solve the problem of hair loss that makes people bald



 

SASP of senescent cells may help solve the problem of hair loss that makes people bald. 

 

What can senescent cells do?

 

Senescent cells cannot proliferate, but can express a special secretion called the senescence-associated secretory phenotype (SASP) . SASP includes a variety of cytokines, growth factors, inflammatory factors, etc., which can be used as intercellular signaling molecules to regulate biological processes such as proliferation, inflammatory response, tissue repair, and immune response of surrounding cells.

 

In other words, although senescent cells stop dividing, they still maintain metabolic activity.

 

Recently, researchers from the University of California, Irvine, found that the SASP of senescent cells may help solve the problem of hair loss that makes people bald [1].

They found that senescent pigment cells in skin moles can stimulate vigorous hair growth. Overexpression of SPP1 (osteopontin) in SASPs of senescent pigment cells induces hair growth in mice, whereas deletion of osteopontin or its receptor CD44 abolishes the effect .

 

Yes, signaling from senescent cells boosts the activity of neighboring stem cells and stimulates tissue renewal . This finding identifies senescent cells and their SASPs as powerful targets for regenerative diseases and has the potential to change our understanding of age-related hair loss .

 

The research was published in Nature.

 

SASP of senescent cells may help solve the problem of hair loss that makes people bald

 

Stem cells have the characteristics of self-renewal and pluripotency, participate in tissue development, maintain normal tissue function and repair damaged tissue, and are the sweet pastry of regenerative medicine and drug screening.

The stem cell niche refers to the specific microenvironment surrounding stem cells, usually composed of multiple cell types and an extracellular matrix that provides signaling molecules, cell-cell interactions, and physical support for stem cells.

 

It has to be said that the skin is an excellent model for studying the stem cell niche. The niche sends a signal to activate the stem cells, and the hair follicle begins a new renewal cycle. While in principle hair follicles can be cycled without external signals, there are thousands of follicles, and making a modest, complete “fur” requires sharing between surrounding non-hair cells signal to achieve.

 

A hairy nevus is a benign lesion on the skin that appears as a darker-skinned brown or black mole with one or more long, coarse hairs. I don’t know if students who are troubled by hair loss have complained, how can the hair on the mole grow so long without losing hair?

 

SASP of senescent cells may help solve the problem of hair loss that makes people bald

Hair follicles around melanocytes enter anagen phase

 

The research team guessed from tumor mutations in melanocytes. Nras or Braf are common gene mutations in melanocytes that are associated with the formation of moles.

At the same time, the mutation induces cell senescence, and the senescent cells secrete SASP containing inflammatory cytokines and growth factors, which changes the ecological niche around the hair follicle and promotes the hair follicle to enter a new renewal cycle.

From gene mutation to hair follicle renewal, the intermediate process may be the key to stimulating mole hair growth.

 

The researchers established Tyr-Nras Q61K and Tyr-Cre ERT2 ;Braf V600E mouse models to mimic congenital and acquired nevi, respectively.

In the normal hair growth cycle of mice, the hair follicle transitions from the quiescent phase to the active growth phase, and then returns to the quiescent phase after the regression phase, and the hair follicle stem cells are in a quiescent state most of the time.

But in Tyr-Nras Q61K mice, it can be observed that there are a large number of senescent melanocytes in the dermis around the hair follicles of the mice, and there are many ectopic anagen hair follicles at any time, and the hair growth of the mice is accelerated .

 

Activation of the Tyr-Cre ERT2 ; Braf V600E gene in Tyr-Cre ERT2;Braf V600E mice using tamoxifen, either early or late in life, resulted in the accumulation of senescent pigment cells and a large number of ectopic anagen hair follicles .

 

SASP of senescent cells may help solve the problem of hair loss that makes people bald

Osteopontin promotes hair growth

 

Through RNA sequencing and single-cell RNA sequencing analysis, the researchers found that the gene expression of Tyr-Nras Q61K mice was significantly different from that of wild-type mice, the expression of various quiescent markers was down-regulated, and the stem cells changed from quiescent to activated .

 

In order to find the key signaling molecules for senescent melanocytes to activate stem cells, the researchers found 598 specifically up-regulated genes in melanocytes in the mutant state through transcriptome sequencing. These genes are related to aging, cell cycle arrest, mitosis, etc. Among them, the osteopontin gene was most significantly up-regulated. Spp1 deficiency can reverse the abnormal hair growth cycle in Tyr-Nras Q61K mice, while Spp1 overexpression can induce hair to enter the growth phase .

 

CD44 is one of the binding sites of osteopontin and is widely expressed in hair follicles. CD44 loss does not significantly affect the number and proliferation of hair follicle stem cells, but reduces the reactivity of stem cells to osteopontin , thereby inhibiting hair growth.

 

SASP of senescent cells may help solve the problem of hair loss that makes people bald

Osteopontin induces hair growth

 

The researchers also found a similar upregulation of osteopontin expression in human congenital hairy nevus, and the expression level of osteopontin was higher in the area of ​​senescent melanocyte accumulation near the hairy pigment nevus .

Human scalp hair follicles were transplanted to melanocyte-deficient mice, and 10 μl of SPP1 or saline was injected into the skin around the transplantation for 3 consecutive days. Compared with the control group, osteopontin accelerated the hair follicles into the anagen phase . Hair also begins to grow vigorously .

 

The study undoubtedly provided new insights into the relationship between senescent cells and tissue stem cells, and proved that senescent cells can have a positive impact on hair follicle stem cells .

 

As for the next research direction, the researchers said, in addition to osteopontin and CD44, are there other molecules in hairy pigmented nevus that induce hair growth? [2]

 

 

 

 

 

 

References:
[1]Wang X, Ramos R, Phan AQ, et al. Signaling by senescent melanocytes hyperactivates hair growth[J]. Nature, 2023, 618(7966): 808-817.

[2] https://www.technologynetworks.com/cell-science/news/common-form-of-hair-loss-could-be-reversed-by-targeting-aged-skin-pigment-cells-375161

SASP of senescent cells may help solve the problem of hair loss that makes people bald

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