title: Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias.
abstract: Aging within the human hematopoietic system associates with various deficiencies and disease states, including anemia, myeloid neoplasms and reduced adaptive immune responses. Similar phenotypes are observed in mice and have been linked to alterations arising at the hematopoietic stem cell (HSC) level. Such an association is, however, less established in human hematopoiesis and prompted us here to detail characteristics of the most primitive human hematopoietic compartments throughout ontogeny. In addition, we also attempted to interrogate similarities between aging human and murine hematopoiesis. Coupled to the transition from human cord blood (CB) to young and aged bone marrow (BM), we observed a gradual increase in frequency of candidate HSCs. This was accompanied by functional impairments, including decreased lymphoid output and reduced proliferative potential. Downstream of human HSCs, we observed decreasing levels of common lymphoid progenitors (CLPs), and increasing frequencies of megakaryocyte/erythrocyte progenitors (MEPs) with age, which could be linked to changes in lineage-affiliated gene expression patterns in aged human HSCs. These findings were paralleled in mice. Therefore, our data support the notion that age-related changes also in human hematopoiesis involve the HSC pool, with a prominent skewing towards the megakaryocytic/erythroid lineages, and suggests conserved mechanisms underlying aging of the blood cell system.
authors.affiliation: Medical Faculty, Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden.|Medical Faculty, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rundberg Nilsson
authors.affiliation: Medical Faculty, Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden.|Medical Faculty, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.affiliation: Medical Faculty, Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden.|Medical Faculty, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Adolfsson
authors.affiliation: Medical Faculty, Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden.|Medical Faculty, Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.affiliation: Medical Faculty, Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden.|Medical Faculty, Lund Stem Cell Center, Lund University, Lund, Sweden.|Department of Pediatric Oncology/Hematology, Skåne University Hospital, Lund, Sweden.
authors.forename: Cornelis Jan
authors.initials: CJ
authors.lastname: Pronk
mesh_terms: D000328:Adult; D000818:Animals; D019070:Cell Lineage; D016922:Cellular Senescence; D041905:Erythroid Cells / Q000166:cytology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D010641:Phenotype; D014158:Transcription, Genetic; D055815:Young Adult