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A cure for a range of blood and immune disorders is in sight, according to researchers who say they’ve solved a mystery of hematopoietic stem cell (HSC) generation.
By studying zebrafish embryos, the investigators found that migratory cells from a region known as the endotome are essential for HSC formation.
The team also discovered some of the signals required for HSC generation and identified genes necessary for endotome formation.
The researchers believe these findings, published in Nature, bring us one step closer to creating viable HSCs in the lab.
“HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body,” said study author Peter Currie, PhD, of the Australian Regenerative Medicine Institute at Monash University in Victoria, Australia.
“Potentially, we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place.”
In an attempt to do just that, Dr Currie and his colleagues studied developing zebrafish. They used high-resolution microscopy to film how HSCs form inside the embryo.
The investigators noted that, in vertebrate embryos, HSCs are initially generated within the dorsal aorta. And previous research showed that signaling relayed from adjacent somites coordinates HSC induction.
Dr Currie and his colleagues found that somite specification of HSCs occurs thanks to an endothelial precursor cell population. These cells arise in a sub-compartment of the zebrafish somite the researchers dubbed “the endotome.”
Endothelial cells from the endotome are specified thanks to activity of the homeobox gene meox1. Specified endotome cells then migrate to and colonize the dorsal aorta, where they induce HSC formation via chemokine signaling that’s activated during endotome formation.
“Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells,” Dr Currie said. “Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.”
“The really exciting thing about these results is that if we can find the signals present in the endotome cells responsible for embryonic HSC formation, then we can use them in vitro to make different blood cells on demand for all sorts of blood-related disorders.”
For the next phase of this research, Dr Currie and his colleagues are attempting to identify more of the molecular cues that trigger HSC production.
A cure for a range of blood and immune disorders is in sight, according to researchers who say they’ve solved a mystery of hematopoietic stem cell (HSC) generation.
By studying zebrafish embryos, the investigators found that migratory cells from a region known as the endotome are essential for HSC formation.
The team also discovered some of the signals required for HSC generation and identified genes necessary for endotome formation.
The researchers believe these findings, published in Nature, bring us one step closer to creating viable HSCs in the lab.
“HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body,” said study author Peter Currie, PhD, of the Australian Regenerative Medicine Institute at Monash University in Victoria, Australia.
“Potentially, we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place.”
In an attempt to do just that, Dr Currie and his colleagues studied developing zebrafish. They used high-resolution microscopy to film how HSCs form inside the embryo.
The investigators noted that, in vertebrate embryos, HSCs are initially generated within the dorsal aorta. And previous research showed that signaling relayed from adjacent somites coordinates HSC induction.
Dr Currie and his colleagues found that somite specification of HSCs occurs thanks to an endothelial precursor cell population. These cells arise in a sub-compartment of the zebrafish somite the researchers dubbed “the endotome.”
Endothelial cells from the endotome are specified thanks to activity of the homeobox gene meox1. Specified endotome cells then migrate to and colonize the dorsal aorta, where they induce HSC formation via chemokine signaling that’s activated during endotome formation.
“Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells,” Dr Currie said. “Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.”
“The really exciting thing about these results is that if we can find the signals present in the endotome cells responsible for embryonic HSC formation, then we can use them in vitro to make different blood cells on demand for all sorts of blood-related disorders.”
For the next phase of this research, Dr Currie and his colleagues are attempting to identify more of the molecular cues that trigger HSC production.
A cure for a range of blood and immune disorders is in sight, according to researchers who say they’ve solved a mystery of hematopoietic stem cell (HSC) generation.
By studying zebrafish embryos, the investigators found that migratory cells from a region known as the endotome are essential for HSC formation.
The team also discovered some of the signals required for HSC generation and identified genes necessary for endotome formation.
The researchers believe these findings, published in Nature, bring us one step closer to creating viable HSCs in the lab.
“HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body,” said study author Peter Currie, PhD, of the Australian Regenerative Medicine Institute at Monash University in Victoria, Australia.
“Potentially, we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place.”
In an attempt to do just that, Dr Currie and his colleagues studied developing zebrafish. They used high-resolution microscopy to film how HSCs form inside the embryo.
The investigators noted that, in vertebrate embryos, HSCs are initially generated within the dorsal aorta. And previous research showed that signaling relayed from adjacent somites coordinates HSC induction.
Dr Currie and his colleagues found that somite specification of HSCs occurs thanks to an endothelial precursor cell population. These cells arise in a sub-compartment of the zebrafish somite the researchers dubbed “the endotome.”
Endothelial cells from the endotome are specified thanks to activity of the homeobox gene meox1. Specified endotome cells then migrate to and colonize the dorsal aorta, where they induce HSC formation via chemokine signaling that’s activated during endotome formation.
“Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells,” Dr Currie said. “Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.”
“The really exciting thing about these results is that if we can find the signals present in the endotome cells responsible for embryonic HSC formation, then we can use them in vitro to make different blood cells on demand for all sorts of blood-related disorders.”
For the next phase of this research, Dr Currie and his colleagues are attempting to identify more of the molecular cues that trigger HSC production.