A single chemical is key to controlling when hair follicle cells divide, and when they die. This discovery could not only treat baldness, but ultimately speed wound healing because follicles are a source of stem cells.
Most cells in the human body have a specific form and function determined during embryonic development that does not change. For example, a blood cell cannot turn into a nerve cell, or vice versa. Stem cells, however, are like the blank tiles in a game of Scrabble; they can turn into other types of cells.
Their adaptability makes them useful for repairing damaged tissue or organs.
“In real life, our new research gets us closer to understanding stem cell behavior, so that we can control it and promote wound healing,” Wang said. This research is detailed in a recent Biophysical Journal article.
The liver and stomach regenerate themselves in response to wounds. However, Wang’s team studied hair follicles because they’re the only organ in humans that regenerates automatically and periodically, even without injury.
The researchers determined how a type of protein, TGF-beta, controls the process by which cells in hair follicles, including stem cells, divide and form new cells, or orchestrate their own death — eventually leading to the death of the whole hair follicle.
As with many chemicals, it is the amount that makes the difference. If the cell produces a certain quantity of TGF-beta, it activates cell division. Too much of it causes apoptosis.
No one is entirely sure why follicles kill themselves. Some hypotheses suggest it is an inherited trait from animals shedding fur to survive hot summer temperatures or trying to camouflage.
“Even when a hair follicle kills itself, it never kills its stem cell reservoir. When the surviving stem cells receive the signal to regenerate, they divide, make new cell and develop into a new follicle,” Wang said.
If scientists can determine more precisely the way TGF-beta activates cell division, and how the chemical communicates with other important genes, it might be possible to activate follicle stem cells and stimulate hair growth.
Because many animals, including humans, possess skin covered with hair, perfect wound healing would require regeneration of hair follicles. Being able to more precisely control levels of TGF-beta could also one day cure baldness, which bothers millions of people all over the world.
“Potentially our work could offer something to help people suffering from a variety of problems,” Wang said.
Hair follicle (HF) is composed of epidermal and dermal compartments, and their interaction plays an important role in HF morphogenesis and growth [1, 2]. The dermal papilla (DP), located at the base of the HF, is a unique tissue surrounded by epithelial matrix cells and is essential in controlling hair growth, formation, and cycling. Human DPCs (hDPCs) exhibit hair inductivity in the early passage and their hair inductivity is declined dramatically during aging.
Therefore, there have been several efforts to induce the hair inductivity of hDPCs. For example, alkaline phosphatase (ALP) overexpression improves the hair inductive capability of cultured hDPCs , and hypoxic culture conditions induced the hair inductivity of hDPCs in the hair reconstitution assay . Microenvironmental reprogramming by three-dimensional (3D) culture enables hDPCs to induce de novo human HF growth .
The tendency to aggregate is a significant characteristic of DPCs, and the ability to aggregate and hair inductivity are reduced after several passages of culture [1, 6]. The loss of the extracellular matrix (ECM) during culture could be responsible for the gradual loss of DPC inductive properties ; however, it has not been demonstrated.
The ECM is a complex and dynamic network of interacting fibrils and associated factors in intimate communication with cells [8, 9]. Although the specific role of the ECM in hair growth regulation is unknown, many studies in other biologic systems have shown that the ECM is involved in processes such as adhesion, cell proliferation, regulation of gene expression, and regulation of growth factor activity. In natural environments in vivo, DP is found at the HF base surrounded by a proteoglycan-rich ECM .
Therefore, it is reasonable to assume that DP interacts with ECM to induce the spheroid formation and regulates hair growth. Collagen is one of the major ECM components and one of the most abundant proteins in humans. Collagen functions are linked to many biological mechanisms involved in homeostasis maintenance and tissue development . However, the involvement of collagen in the hair inductivity of hDPCs has not been determined.
In most cells, the fundamental functions of transforming growth factor-β (TGF-β) isoforms are growth control and ECM deposition . Especially during fetal development, TGF-βs are found in a broad range of organs, such as epithelium, myocardium, cartilage, and bone of extremities, and the nervous system, suggesting its critical functions in organogenesis [13, 14]. In HF physiology, TGF-βs have been shown to exert unique multidirectional effects, such as inductive and suppressive effects on hair growth. For example, TGF-β1 blocks anagen and induces catagen , thereby inhibiting hair growth .
TGF-β2 induces premature HF regression in adult hair cycling [17, 18]. In contrast, TGF-β1 and TGF-β2 stimulate the proliferation of outer root sheath keratinocytes [19, 20]. It is of interest that TGF-β2 is required for hair folliculogenesis [21, 22]. Studies involving mice deficient in different TGF-β isoforms have shown that TGF-β2 is required for murine HF development, whereas TGF-β1 and TGF-β3 do not contribute significantly to this process . TGF-β2 is primarily produced in the DP region and stimulates the proliferation of HF stem cells (HFSCs) by counteracting bone morphogenetic protein-mediated quiescence in the niche .
In this study, we investigated whether collagen expression changes in hDPCs are involved in the senescence and hair inductivity of hDPCs and further examined the underlying molecular mechanism of collagen regulation. This study reported that TGF-β2 inhibited the cellular senescence and induced spheroid formation of hDPCs by upregulating COL13A1 and COL15A1 expression.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436940/
Original Research: Closed access.
“A probabilistic Boolean model on hair follicle cell fate regulation by TGF-β” by Qixuan Wang et al. Biophysical Journal