Although scientists know that stem cells work by repairing damaged cells and sometimes renewing normal ones, little is known about where they originate when the embryo is developing. Now, a team of scientists at The Rockefeller University have identified a mechanism that stimulates developing cells to become stem cells, which helps explain the communication process between cells as this happens and could shed light on potential skin cancer treatments.
"While adult stem cells are increasingly well-characterized, we know little about their origins. Here, we show that in the skin, stem cell progenitors of the hair follicle are specified as soon as the cells within the single-layered embryonic epidermis begin to divide downward to form an embryonic hair bud," Elaine Fuchs, who co-authored the research, said in a press release. "This timing was much earlier than previously thought, and gives us new insights into the establishment of these very special cells."
Previous research has shown that stem cells are instructed by nearby cells to either remain a stem cell or become a different cell type, but the origin of these instructive cells was always a mystery. Using a mouse hair follicle, Fuchs and her team examined the cell divisions that occur when it is first forming. They found that for each division of the cells, one daughter cell remained while the other moved to a different layer, revealing that stem cells may exist before their instructive cells.
Fuchs and her team continued to examine these cells, looking at two daughter cells that ended up in different locations in order to determine what kind of cell signals determined their fate. They found that the environment that the daughter cell fled to always had low levels of WNT signaling, which is known to play a role in the process of embryonic development. Conversely, the environment where the daughter cell remained had high levels of WNT signaling. The team also found that WNT levels also affected how cells responded to SHH signaling - only in low-WNT environments do cells respond to SHH signaling, which subsequently stimulates the cells to turn into stem cells.
"These cells must leave home, they must leave the environment with high WNT signaling, to become stem cells," said Tamara Ouspenskaia, first author of the study. "We observed that SHH, which actually comes from the cells with high WNT signaling, is essential in helping the cells leave. So in order for this escapee cell to become a stem cell, it needs to receive an SHH signal from its sister cell at home telling it 'you're the stem cell.'"
The findings were published in the Jan. 14 issue of Cell.
