Hematopoietic stem cells are critical to the body’s function for many reasons – one of them is owing to their ability to differentiate into blood cells and platelets. A new study identified a gene that regulates such adult hematopoietic stem cells.
Researchers from the Stowers Institute for Medical Research, Dr. Linheng Li and first author Dr. Pengxu Qian, along with other collaborators, discovered how the mammalian imprinted gene Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells’ mitochondria. The gene resides within the Dlk1-Gtl2 locus.
Imprinted genes are those genes inherited from the parents. The paternally inherited gene’s expression promotes growth, while the expression of the maternally inherited allele’s suppresses it.
When Gtl2 is expressed from the maternally-inherited allele, it inhibits metabolic activity, thereby protecting adult stem cells.
The authors zoned in on Gtl2 by looking at 17 hematopoietic stem cell types.
Moreover, the authors found that loss of Dlk1-Gtl2 imprinting leads to functional defects in fetal liver hematopoietic stem cells. Indeed, abnormalities in Glt2 (studied by deleting the gene) were found to be associated with detrimental consequences which include cell death.
On a more global level, miRNAs of the Dlk1-Gtl2 locus suppress components of the entire PI3K-mTOR pathway.
This finding is important as it has led to the identification of a gene (Gtl2) that can act as biomarkers for identifying different hematopoietic stem cell states.
The manuscript, titled “The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism,” was published in Cell Stem Cell. Read it here.