Stem cells are totipotent and can remain dormant or become active to regenerate cells of a specific tissue. Either of these actions is the result of niche signals. In melanocytes, such niche signals may be altered to direct stem cells in the hair follicles of the skin into a hyperactive state, causing hair to grow in excess.
Congenital melanocytic nevi (CMN), which may also be referred to as human skin nevi, are noncancerous skin lesions that typically present at birth or within the first few weeks of life. These nevi are dark in color due to the prevalence of melanocytes and frequently exhibit excessive hair growth, the latter of which may be due to the hyperactivity of hair stem cells in these nevi.
Stem cells can be found in various areas of the skin, including hair follicles. Here, hair stem cells exhibit cyclic shedding and hair growth, which is initiated by the cyclic renewal of progenitors in the follicle.
This is in response to signaling between follicle and non-hair cells, including skin adipocytes and adipose progenitors in the niche, characterized by specialized fibroblasts in the dermal papilla. These cells occur in proximity and utilize common regulatory pathways to facilitate hair growth. Various immune cells within the skin also produce signals that modify hair growth.
A new study published in the journal Nature investigated the mechanism responsible for the excessive hair growth often observed in hairy-pigmented nevi. Nevi arise as a result of oncogene mutations in the Braf pathway within skin melanocytes. These mutated cells first expand but soon thereafter enter oncogene-induced senescence (OIS).
The end of this process is a circumscribed lesion with relatively higher numbers of senescent melanocytes. These cells exhibit a distinct pattern of secretion forming the senescence-associated secretory phenotype (SASP), which includes a number of inflammatory cytokines and growth factors that are key to normal developmental pathways, repair processes, cellular reprogramming, and tumor progression.
What did the study show?
Clusters of senescent melanocytes, but not normal melanocytes, in a hairy nevus produced signals to epithelial hair stem cells, subsequently inducing excessive hair growth. Melanocyte OIS was crucial for producing increased hair growth rates in hairy pigmented nevi in mouse models.
Signaling by senescent melanocytes caused stem cells to transition from quiescent to hyperactive. The loss of quiescence was associated with the expression of senescence by melanocytes, which was reflected in the transcriptional and compositional profile of the stem cells that ultimately contributed to the overgrowth of hair.
Melanocytes in a nevus secreted a unique set of factors that included higher-than-expected levels of signaling factors. The main component of this change in the secretome was a marked rise in osteopontin production in clusters of dermal melanocytes associated with the nevus. Osteopontin is required for hair growth and induces this process, even in the absence of other factors, both in pigmented hairy nevi and during wound healing.
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For example, an injection of osteopontin in mice causes hair to grow rapidly and thickly. The same effect is observed following the manipulation of the rate of transcription of this hormone.
Osteopontin is recognized by the CD44 receptor on epithelial hair stem cells, which mediates the effect of osteopontin in the hyperactivation of hair growth in the nevus. When either this hormone or its receptor is knocked out, the hair growth occurring in response to the signaling by dermal melanocytes is reversed.
Hairy nevi in humans were found to overexpress osteopontin, thus leading to the formation of new hair follicles and hair growth activation.
What are the implications?
Although broad accumulation of senescent cells is detrimental for the regenerative capacity of tissue, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal.”
Senescent cells contribute to the aging and death of tissues; however, they also have beneficial effects on the growth of tissues. For example, senescent cells occur in embryonic tissues and may regulate or direct growth. Similarly, these cells may be observed in injured adult tissues, where they promote repair processes.
Signaling by senescent cells is a physiological growth-promoting pathway, as observed in the current study, where hair growth occurs in response to melanocyte senescence within a hairy pigmented nevus. The result of senescence may depend on the SASP and varies with the cell of origin or mechanism of senescence. Osteopontin is the major SASP component secreted by senescent dermal melanocytes that is responsible for excessive hair growth.
Future studies are needed to understand the interaction between stem cells in hair follicles and senescent dermal melanocytes within the nevi. This type of research will answer critical questions, such as why oncogene mutations produce senescence in dermal melanocytes adjacent to the hair follicles in mice but not within the follicle. Does the hair follicle counteract the effects of senescent cells?
The study findings indicate a peculiar pathway of regulation of hair growth by hair stem cells that is mediated by dermal melanocytes in senescence. This points to the potential for using senescent cells and their secretomes to correct regenerative disorders.
Journal reference:
Wang, X., Ramos, R., Phan, A. Q., et al. (2023). Signalling by senescent melanocytes hyperactivates hair growth. Nature. doi:10.1038/s41586-023-06172-8.
VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.
Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.
In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.
The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.
Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”
Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”
This report by The Canadian Press was first published Sept. 16, 2024
The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.
It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.
Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”
Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.
Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.
A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.
On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.
Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”
But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”
“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.
Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.
Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.
Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.
“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.
“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”
This report by The Canadian Press was first published Sept. 13, 2024.
Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
