University of Michigan researchers have for the first time identified a gene, Sox17, which is required for the maintenance of blood-forming stem cells in foetal mice, but not in adult mice.
A study conducted by them has added to mounting evidence that stem cells in the developing foetus are distinct from both embryonic and adult stem cells.
In the last several years, stem cell researchers have realized that foetal stem cells comprise a separate class. They have recognized that foetal blood-forming stem cells in umbilical cord blood behave differently than adult blood-forming stem cells after transplantation into patients.
Sean Morrison, director of the U-M Center for Stem Cell Biology and a Howard Hughes Medical Institute investigator, says that the new findings may also lead to a deeper understanding of diseases such as childhood leukaemia, cancers that afflict blood-forming cells and hijack normal stem cell self-renewal mechanisms.
"One of the next questions in our cross hairs is whether Sox17 gets inappropriately activated in certain childhood leukemias---and that's an idea that nobody had in their mind before this work. If it's true, it'll give us a new target for cancer," said Morrison.
"Identification of Sox17 could also facilitate efforts to form blood-forming stem cells from human embryonic stem cells, a goal that could enhance bone marrow transplantation," said Injune Kim, lead author of the study, reported in the journal Cell.
In the latest study, the researchers deleted the Sox17 gene in laboratory mice to test whether Sox17 was functionally important for foetal and neonatal blood-forming stem cells. This led to the loss of foetal and neonatal, but not adult, haematopoietic stem cells.
The researchers then transplanted replacement foetal or neonatal blood-forming cells, some containing the Sox17 gene and others lacking it, into the mice. The mice that received Sox17-bearing cells were able to regenerate their blood systems, while those receiving cells lacking Sox17 could not.
"Sox17 is really a critical player. If you knock it out in mice, they never develop a blood system. They never form blood cells," Morrison said.