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Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.
Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.
This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.
“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.
Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.
Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.
The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.
“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.
“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”
Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).
“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”
“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.” 
Image by John Perry
Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.
Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.
This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.
“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.
Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.
Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.
The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.
“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.
“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”
Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).
“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”
“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.”
Image by John Perry
Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.
Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.
This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.
“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.
Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.
Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.
The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.
“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.
“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”
Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).
“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”
“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.”