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Protein promotes hematopoietic regeneration

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Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

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HSCT preparation

Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

HSCT preparation

Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

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