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A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said. 
Photo by Aaron Logan
A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.
Photo by Aaron Logan
A genome-wide association study conducted in mice has provided new insights regarding hematopoietic stem/progenitor cells (HSPCs).
Researchers screened more than 100 mouse strains and found great variation in the frequency of 3 HSPC subpopulations.
The team also showed that Hopx, a gene that was not known to influence HSPC biology, regulates the frequency and function of HSPCs.
The researchers recounted these findings in Stem Cell Reports.
Hooman Allayee, PhD, of the University of Southern California in Los Angeles, and his colleagues screened 108 strains of mice known as the hybrid mouse diversity panel.
The screen revealed 3 HSPC subpopulations whose frequency varied greatly among the different mouse strains. The frequency of these HSPCs—Lin-Sca-1+c-Kit+ (LSK) cells, LSKCD150-CD48- cells, and LSKCD150+CD48- cells—varied roughly 120-fold to 300-fold.
The researchers then found that these 3 cell populations were significantly correlated with each other and with certain hematologic parameters. There was a significant positive association between LSK cells and total white blood cell (P=0.005), monocyte (P<0.0001), and lymphocyte counts (P=0.04).
LSKCD150-CD48- cells had a significant negative correlation with lymphocyte (P=0.006) and monocyte counts (P=0.002) as well as a significant positive association with granulocyte counts (P=0.0002).
LSKCD150+CD48- cells had a significant positive correlation with total white blood cell count (P=0.02) and a significant negative association with mean corpuscular hemoglobin (P<0.001).
Additional experiments showed that the frequency and function of LSKCD150-CD48- cells were regulated by Hopx, but the gene did not appear to impact LSK or LSKCD150+CD48- cells.
Mice lacking the Hopx gene had significantly lower numbers of LSKCD150-CD48- cells than wild-type mice, but LSK and LSKCD150+CD48- counts were similar between Hopx-/- and wild-type mice.
The researchers also conducted competitive repopulation assays with HSCs from Hopx-/- and wild-type mice. HSCs from Hopx-/- mice had significantly impaired engraftment at 16 weeks after transplant, which extended to 24 weeks.
Dr Allayee and his colleagues said that identifying this new role for Hopx could have clinical implications, and this research suggests the hybrid mouse diversity panel can be used to find genes that would otherwise go unnoticed.
“This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Dr Allayee said.