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Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.
Yamamoto, Ryo; Wilkinson, Adam C; Ooehara, Jun; Lan, Xun; Lai, Chen-Yi; Nakauchi, Yusuke; Pritchard, Jonathan K; Nakauchi, Hiromitsu.
Afiliación
  • Yamamoto R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA; Division of Stem Cell Therapy, Center for Stem Cell Biol
  • Wilkinson AC; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
  • Ooehara J; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • Lan X; Department of Genetics, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
  • Lai CY; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • Nakauchi Y; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • Pritchard JK; Department of Genetics, Stanford University, Stanford, CA, USA; Department of Biology, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
  • Nakauchi H; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA; Division of Stem Cell Therapy, Center for Stem Cell Biol
Cell Stem Cell ; 22(4): 600-607.e4, 2018 04 05.
Article en En | MEDLINE | ID: mdl-29625072
ABSTRACT
Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Envejecimiento / Células Madre Hematopoyéticas / Trasplante de Células Madre Hematopoyéticas Límite: Animals Idioma: En Revista: Cell Stem Cell Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Asunto principal: Envejecimiento / Células Madre Hematopoyéticas / Trasplante de Células Madre Hematopoyéticas Límite: Animals Idioma: En Revista: Cell Stem Cell Año: 2018 Tipo del documento: Article