From the life of hair follicles: eggs teach a chicken
Stem cells are "turned on" by their own offspring
NanoNewsNet based on the materials of The Rockefeller University: Stem cell progeny tell their parents when to turn onStem cells "turn off" and "turn on", sometimes dividing to produce offspring, and sometimes resting.
But scientists do not yet fully understand what causes cells to move from an active state to a resting state and vice versa.
To determine what activates stem cells, scientists at the Elaine Fuchs Laboratory of Mammalian Cell Biology and Development at Rockefeller University focused their attention on hair follicle cells. The researchers found that the signal to the resting stem cells of hair follicles to go into an active state is given by stem cell descendants, known as Transit-Amplifying Cells, or TACs.
"TACs form many types of mammalian stem cells. They are an intermediate link between stem cells and their final product: fully differentiated blood cells, skin cells, etc.," explains Ya–Chieh Hsu, the first author of the article published in the journal Cell. "In the past, TACs were considered a population of cells that passively "churn out" a large number of tissue cells. No one expected them to play a regulatory role."
Fuchs and Hsu went further and identified the signal sent by TACs. They identified a cell division-stimulating protein called Sonic Hedgehog, which plays a role in the embryonic development of the brain, eyes and limbs.
Stem cells are valuable from a medical point of view, as they have the potential to create a number of specialized cells that perform certain functions. The formation of these differentiated descendants by stem cells is crucial for normal growth and recovery. Many tissues have two stem cell populations. The cells of one of them divide rarely (they are known as dormant), and the cells of the other are more prone to reproduction and are known as primed stem cells. Regardless of the frequency of proliferation, most human stem cells do not produce differentiated offspring directly; instead, they give rise to an intermediate proliferating population – TACs.
The hair follicle, the tiny organ that forms the hair, forms a narrow cavity in the skin. It cycles through the phases of growth, destruction and rest. When entering the growth phase, the population of primed stem cells always divides first, forming TACs that form clusters in the lower part of the hair follicle. The proliferation of primed stem cells prepares the ground for the next round of hair growth – a process that ensures the replacement of those lost over time. Proliferating TACs create the hair shaft, as well as all the cells surrounding the hair under the skin, forming a follicle as such.
Fuchs and Hsu believed from the very beginning that both TACs and the Sonic Hedgehog protein play a role in hair regeneration. "We noticed that the population of primed stem cells is activated early and forms TACs, while the population of dormant stem cells is activated only after the formation of TACs. This correlation made us look for the signal sent by TACs. As we subsequently demonstrated, this signal is the Sonic Hedgehog protein," Fuchs explains.
In experiments described in the journal Cell (Transit-Amplifying Cells Orchestrate Stem Cell Activity and Tissue Regeneration), Hsu deprived TACs in the hair follicles of adult mice of the ability to synthesize Sonic Hedgehog by knocking out the gene encoding it. As a result, the proliferation of both hair follicle stem cells and their TACs was disrupted. In addition, the researchers have shown that Sonic Hedgehog is required for the proliferation of a population of resting stem cells.
In the picture: Scientists have found that a signal sent by cells called Transit-Amplifying Cells (TACs) activates hair follicle stem cells. Both cell types are shown in green (in the upper image), with TACs forming clusters at the bottom of the follicle. This signal is the Sonic Hedgehog protein. By disabling it, the researchers stopped the growth and regeneration of hair, which is shown in the bottom picture.
(Photo: The Rockefeller University)
Surprisingly, when Hsu blocked the ability of resting stem cells to respond to Sonic Hedgehog, hair growth continued, but with each turn of the cycle, the follicles became shorter, the populations of resting and primed stem cells decreased until hair regeneration stopped completely. According to the researchers, these events are very similar to what happens with baldness in men. Although the basis of this disorder may be higher than Sonic Hedgehog, the study by Fuchs and Hsu explains hair loss in a new way, and in the long term it will be necessary to develop new treatments, they believe.
TACs is a stage in the development of various stem cell lines, and the researchers claim that although other signaling molecules may play the role of the Sonic Hedgehog protein, TACs themselves most likely function in the same way in other tissues, for example, in the blood and intestines.
"In most adult tissues," Fuchs explains, "our stem cells need to be able to respond quickly to damage. With TACs as rheostats, this process can be tightly regulated to provide the right amount of new tissue for wound healing. Thus, TACs can no longer be considered as a passive, intermediate link of the stem cell line. Rather, they are a key signaling center coordinating tissue regeneration."
Portal "Eternal youth" http://vechnayamolodost.ru04.06.2014