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Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.
However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.
The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.
By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.
“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.
Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.
Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.
Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.
The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.
The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.
The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.
In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant. 
Photo courtesy of NHS
Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.
However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.
The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.
By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.
“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.
Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.
Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.
Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.
The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.
The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.
The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.
In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant.
Photo courtesy of NHS
Researchers have discovered a genetic switch that could increase the supply of hematopoietic stem cells (HSCs) derived from cord blood, according to a paper published in Cell Stem Cell.
However, experiments in mice suggest that flipping the switch may also spur the development of myeloproliferative disease.
The researchers explained that, when an HSC divides, it produces multipotent progenitor (MPP) cells immediately downstream that retain the ability to differentiate but have lost the ability to self-renew.
By analyzing murine and human models of hematopoiesis, the team discovered that a microRNA, miR-125a, controls self-renewal and is normally switched on in HSCs but turned off in MPPs.
“Our work shows that if we artificially throw the switch on in those downstream cells [MPPs], we can endow them with stemness, and they basically become stem cells and can be maintained over the long term,” said study author John Dick, PhD, of Princess Margaret Cancer Centre at University Health Network in Toronto, Ontario, Canada.
Specifically, Dr Dick and his colleagues found that overexpression of miR-125a induced stem cell potential in both human MPPs and an as-yet-unidentified population within the CD34+38+ committed progenitor compartment.
Overexpression of miR-125a had a similar effect in murine MPPs. When the researchers transplanted these MPPs into recipient mice, the cells exhibited increased self-renewal and generated high levels of multi-lineage reconstitution for up to 16 weeks after transplant.
Unfortunately, when the miR-125a-overexpressed MPPs were transplanted into secondary and tertiary recipient mice, the animals developed symptoms of a myeloproliferative disease.
The researchers said this result is in line with findings from previous studies and has been shown to be dependent upon sustained expression of miR-125a and dosage.
The current study suggested that the miR-125a-induced myeloproliferative disease occurs, in part, as a function of replicative stress.
The researchers therefore speculated that, with careful titration of miR-125a levels, it may be possible to reap the beneficial self-renewal effects of miR-125a without inducing myeloproliferative disease.
In fact, the team hopes that, in the future, approaches combining miR-125a-modified MPPs with existing small-molecule compounds will enable the expansion of cord blood units for transplant.