title: Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions.
abstract: The ability of cells to count and remember their divisions could underlie many alterations that occur during development, aging, and disease. We tracked the cumulative divisional history of slow-cycling hematopoietic stem cells (HSCs) throughout adult life. This revealed a fraction of rarely dividing HSCs that contained all the long-term HSC (LT-HSC) activity within the aging HSC compartment. During adult life, this population asynchronously completes four traceable symmetric self-renewal divisions to expand its size before entering a state of dormancy. We show that the mechanism of expansion involves progressively lengthening periods between cell divisions, with long-term regenerative potential lost upon a fifth division. Our data also show that age-related phenotypic changes within the HSC compartment are divisional history dependent. These results suggest that HSCs accumulate discrete memory stages over their divisional history and provide evidence for the role of cellular memory in HSC aging.
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bernitz
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Huen Suk
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Mathematical Sciences, University of Southampton, Southampton SO17 1BJ, UK; Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: MacArthur
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, CA 92121, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Sieburg
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA. Electronic address: kateri.moore@mssm.edu.
authors.forename: Kateri
authors.initials: K
authors.lastname: Moore
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D002455:Cell Division; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism
chemical_list: D040201:Platelet Membrane Glycoprotein IIb
keywords: aging; cell division counting; cellular memory; dormancy; hematopoietic stem cells