title: Angiogenin Promotes Hematopoietic Regeneration by Dichotomously Regulating Quiescence of Stem and Progenitor Cells.
abstract: Regulation of stem and progenitor cell populations is critical in the development, maintenance, and regeneration of tissues. Here, we define a novel mechanism by which a niche-secreted RNase, angiogenin (ANG), distinctively alters the functional characteristics of primitive hematopoietic stem/progenitor cells (HSPCs) compared with lineage-committed myeloid-restricted progenitor (MyePro) cells. Specifically, ANG reduces the proliferative capacity of HSPC while simultaneously increasing proliferation of MyePro cells. Mechanistically, ANG induces cell-type-specific RNA-processing events: tRNA-derived stress-induced small RNA (tiRNA) generation in HSPCs and rRNA induction in MyePro cells, leading to respective reduction and increase in protein synthesis. Recombinant ANG protein improves survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPCs in transplantation. Thus, ANG plays a non-cell-autonomous role in regulation of hematopoiesis by simultaneously preserving HSPC stemness and promoting MyePro proliferation. These cell-type-specific functions of ANG suggest considerable therapeutic potential.
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA; Graduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
authors: Kevin A
authors: KA
authors: Goncalves
authors: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors: Lev
authors: L
authors: Silberstein
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors: Shuping
authors: S
authors: Li
authors: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors: Nicolas
authors: N
authors: Severe
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors: Miaofen G
authors: MG
authors: Hu
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA; Graduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
authors: Hailing
authors: H
authors: Yang
authors: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: david_scadden@harvard.edu.
authors: David T
authors: DT
authors: Scadden
authors: Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA; Graduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA. Electronic address: guo-fu.hu@tufts.edu.
authors: Guo-Fu
authors: GF
authors: Hu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*
chemical_list: D022661:RNA, Untranslated; D012343:RNA, Transfer; C046366:angiogenin; D012259:Ribonuclease, Pancreatic