title: Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate.
abstract: Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization that individual HSCs might be preset differentially already from young age, HSCs might also age asynchronously. Evaluating the prospects for HSC rejuvenation therefore ultimately requires approaching those HSCs that are functionally affected by age. Here we combine genetic barcoding of aged murine HSCs with the generation of induced pluripotent stem (iPS) cells. This allows us to specifically focus on aged HSCs presenting with a pronounced lineage skewing, a hallmark of HSC ageing. Functional and molecular evaluations reveal haematopoiesis from these iPS clones to be indistinguishable from that associating with young mice. Our data thereby provide direct support to the notion that several key functional attributes of HSC ageing can be reversed.
authors.affiliation: Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Wahlestedt
authors.affiliation: Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Erlandsson
authors.affiliation: Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.
authors.forename: Trine
authors.initials: T
authors.lastname: Kristiansen
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.affiliation: Biotech Research and Innovation Centre, Biomedical Institute, University of Copenhagen, 2200 Copenhagen, Denmark.|Core Facility for Transgenic Mice, Department of Biomedical Sciences University of Copenhagen, The Panum Institute, 6.4, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.affiliation: Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Palo Alto, California 94305, USA.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.|StemTherapy, Lund University.
authors.forename: Joan
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Core Facility for Transgenic Mice, Department of Biomedical Sciences University of Copenhagen, The Panum Institute, 6.4, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Javier
authors.initials: J
authors.lastname: Martin-Gonzalez
authors.affiliation: Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.|StemTherapy, Lund University.
authors.forename: David
authors.initials: D
authors.lastname: Bryder
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D002999:Clone Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism