Summary: Researchers discovered how the TGF-beta protein controls the process by which hair follicles, including stem cells, divide and form new cells or orchestrate apoptosis. The findings could provide new treatment options for baldness and therapies to speed up wound healing.
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 science fiction when characters heal quickly from injuries, the idea is that stem cells allowed it,” said UC Riverside mathematical biologist and study co-author Qixuan Wang.
“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.
“TGF-beta has two opposite roles. It helps activate some hair follicle cells to produce new life, and later, it helps orchestrate apoptosis, the process of cell death,” Wang said.
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.
About this baldness and genetics research news
Author: Jules Bernstein Source: UCR Contact: Jules Bernstein – UCR Image: The image is credited to Helpaeatcontu
A probabilistic Boolean model on hair follicle cell fate regulation by TGF-β
Hair follicles (HFs) are mini skin organs that undergo cyclic growth. Various signals regulate HF cell fate decisions jointly. Recent experimental results suggest that transforming growth factor beta (TGF-ββ) exhibits a dual role in HF cell fate regulation that can be either anti- or pro-apoptosis.
To understand the underlying mechanisms of HF cell fate control, we develop a novel probabilistic Boolean network (pBN) model on the HF epithelial cell gene regulation dynamics. First, the model is derived from literature, then refined using single-cell RNA sequencing data.
Using the model, we both explore the mechanisms underlying HF cell fate decisions and make predictions that could potentially guide future experiments: 1) we propose that a threshold-like switch in the TGF-ββ strength may necessitate the dual roles of TGF-ββ in either activating apoptosis or cell proliferation, in cooperation with bone morphogenetic protein (BMP) and tumor necrosis factor (TNF) and at different stages of a follicle growth cycle; 2) our model shows concordance with the high-activator-low-inhibitor theory of anagen initiation; 3) we predict that TNF may be more effective in catagen initiation than TGF-ββ, and they may cooperate in a two-step fashion; 4) finally, predictions of gene knockout and overexpression reveal the roles in HF cell fate regulations of each gene.
Attractor and motif analysis from the associated Boolean networks reveal the relations between the topological structure of the gene regulation network and the cell fate regulation mechanism.
A discrete spatial model equipped with the pBN illustrates how TGF-ββ and TNF cooperate in initiating and driving the apoptosis wave during catagen.