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Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.” 
Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.”
Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.”