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Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood. 
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.
Preclinical research suggests hepatic leukemia factor (HLF) protects hematopoietic stem cells (HSCs) by helping them maintain quiescence.
Researchers found that HLF-deficient HSCs were more sensitive than wild-type HSCs to chemotherapy and irradiation.
After transplantation in mice, HLF-deficient HSCs were less able than wild-type HSCs to reconstitute hematopoiesis.
These findings were published in Cell Reports.
“The study confirms several previous studies that show the HLF gene’s significance in blood formation,” said study author Mattias Magnusson, PhD, of Lund University in Sweden.
“Identifying the factors that control blood stem cells provides knowledge needed to be able to propagate the stem cells outside the body. This has long been one of the major goals in the blood stem cell field, as it would increase possibilities for blood stem cell transplantation when, for example, there is a shortage of stem cells or donors. In addition, we will increase our understanding of how leukemia arises.”
Previous research by Dr Magnusson and his colleagues suggested that HLF may regulate HSCs in both normal and malignant hematopoiesis.
With the current study, the researchers found that HLF was “dispensable for steady-state hematopoiesis.” In fact, HLF-knockout mice had “essentially normal hematopoietic parameters” in steady-state conditions.
However, when HLF-deficient HSCs were serially transplanted in mice, the cells showed a reduction in regenerative potential, when compared to wild-type HSCs.
Additionally, mice with HLF-deficient HSCs exhibited increased sensitivity to the myeloablative agent 5-fluorouracil and reduced survival after sublethal irradiation, as compared to control mice.
“It’s surprising that the mice [initially] lived a normal life without the HLF gene, but when they had an acute need for new blood after an external damage such as cytostatic treatment, the mice did not survive,” Dr Magnusson said.
“All the blood stem cells were eliminated by the treatment, as they were active rather than in a resting state. Without the HLF gene, the blood stem cells were no longer protected against cytostatic treatment or other types of stress such as transplantation.”
Taking their findings together, Dr Magnusson and his colleagues concluded that HLF is a “critical” regulator of HSC quiescence and “essential” for maintaining HSCs’ ability to produce new blood.