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in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.
in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.
in the bone marrow
The Dlk1-Gtl2 locus plays a critical role in protecting hematopoietic stem cells (HSCs), according to preclinical research.
The study suggests the mammalian imprinted gene Gtl2, located on mouse chromosome 12qF1, protects adult HSCs by restricting metabolic activity in the cells’ mitochondria.
This work indicates that Gtl2 may be useful as a biomarker to determine if cells are normal or potentially cancerous.
Linheng Li, PhD, of the Stowers Institute for Medical Research in Kansas City, Missouri, and his colleagues described this research in Cell Stem Cell.
The researchers knew that the Dlk1-Gtl2 locus produces multiple non-coding RNAs from the maternally inherited allele, including the largest microRNA cluster in the mammalian genome.
“Most of the non-coding RNAs at the Gtl2 locus have been documented to function as tumor suppressors to maintain normal cell function,” said study author Pengxu Qian, PhD, also from the Stowers Institute for Medical Research.
However, the role of this locus in HSCs was unclear. So the team studied HSCs in mice. They used transcriptome profiling to analyze 17 hematopoietic cell types.
The analyses revealed that non-coding RNAs expressed from the Gtl2 locus are predominantly enriched in fetal liver HSCs and adult long-term HSCs, and these non-coding RNAs sustain long-term HSC functionality.
Gtl2’s megacluster of microRNA suppresses the mTOR signaling pathway and downstream mitochondrial biogenesis and metabolism, thus blocking reactive oxygen species (ROS) that can damage adult stem cells.
When the researchers deleted the Dlk1-Gtl2 locus from the maternally inherited allele in HSCs, they observed increases in mitochondrial biogenesis, metabolic activity, and ROS levels, which led to cell death.
Dr Li said these findings suggest Gtl2 could be used as a biomarker because it could help label dormant (or reserve) stem cells in normal or potentially cancerous stem cell populations.
The addition of a fluorescent tag to the Gtl2 locus could allow researchers to mark other adult stem cells in the gut, hair follicle, muscle, and neural systems.