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Publication

Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.

Cell stem cell | 2018

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.

Pubmed ID: 29625072 RIS Download

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Associated grants

Agency: NHGRI NIH HHS, United States
Id: U01 HG009431
Agency: Howard Hughes Medical Institute, United States

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

BioLegend (tool)

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Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.

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Miltenyi Biotec (tool)

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CD117 (c-Kit) Monoclonal Antibody (2B8), PE-Cyanine7, eBioscience (antibody)

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Anti-APC MicroBeads (antibody)

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CD41a Monoclonal Antibody (eBioMWReg30 (MWReg30)), eFluor™ 450, eBioscience (antibody)

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TER-119 Monoclonal Antibody (TER-119), APC, eBioscience (antibody)

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CD8a Monoclonal Antibody (53-6.7), APC, eBioscience (antibody)

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CD4 Monoclonal Antibody (RM4-5), APC, eBioscience (antibody)

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APC anti-mouse CD3 (antibody)

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CD45R (B220) Monoclonal Antibody (RA3-6B2), APC-eFluor™ 780, eBioscience (antibody)

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CD11b Monoclonal Antibody (M1/70), FITC, eBioscience (antibody)

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Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), FITC, eBioscience (antibody)

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Pacific Blue(TM) anti-mouse CD45.2 (antibody)

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PE/Cyanine7 anti-mouse CD45.1 (antibody)

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NOT AN ANTIBODY Streptavidin APC-eFluor 780 100 ug (antibody)

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FITC anti-mouse CD16/32 (antibody)

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PE anti-mouse CD16/32 (antibody)

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PE/Cyanine7 anti-mouse CD127 (IL-7Ralpha) (antibody)

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CD135 (Flt3) Monoclonal Antibody (A2F10), PerCP-eFluor™ 710, eBioscience (antibody)

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CD135 (Flt3) Monoclonal Antibody (A2F10), PE, eBioscience (antibody)

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CD135 (Flt3) Monoclonal Antibody (A2F10), APC, eBioscience (antibody)

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This monoclonal targets CD135 (Flt3)

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APC/Cyanine7 anti-mouse CD48 (antibody)

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This monoclonal targets CD48

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PE/Cyanine7 anti-mouse Ly-6A/E (Sca-1) (antibody)

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This monoclonal targets Ly-6A/E

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Brilliant Violet 510(TM) anti-mouse Ly-6A/E (Sca-1) (antibody)

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This monoclonal targets Ly-6A/E

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Ly-6A/E (Sca-1) Monoclonal Antibody (D7), Alexa Fluor™ 700, eBioscience (antibody)

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This monoclonal targets Ly-6A/E (Sca-1)

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Ly-6A/E (Sca-1) Monoclonal Antibody (D7), PerCP-Cyanine5.5, eBioscience (antibody)

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This monoclonal targets Ly-6A/E (Sca-1)

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Ly-6A/E (Sca-1) Monoclonal Antibody (D7), PE-Cyanine7, eBioscience (antibody)

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This monoclonal targets Ly-6A/E (Sca-1)

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CD41a Monoclonal Antibody (eBioMWReg30 (MWReg30)), FITC, eBioscience (antibody)

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This monoclonal targets CD41a

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Brilliant Violet 421(TM) anti-mouse CD41 (antibody)

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APC anti-mouse CD150 (SLAM) (antibody)

RRID:AB_493460

This monoclonal targets CD150

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Brilliant Violet 421(TM) anti-mouse CD150 (SLAM) (antibody)

RRID:AB_2650881

This monoclonal targets CD150

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CD34 Monoclonal Antibody (RAM34), FITC, eBioscience (antibody)

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This monoclonal targets CD34

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CD34 Monoclonal Antibody (RAM34), Alexa Fluor™ 700, eBioscience (antibody)

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Pacific Blue(TM) anti-mouse CD117 (c-kit) (antibody)

RRID:AB_493476

This monoclonal targets CD117

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CD117 (c-Kit) Monoclonal Antibody (2B8), APC, eBioscience (antibody)

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This monoclonal targets CD117 (c-Kit)

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CD5 Monoclonal Antibody (53-7.3), Biotin, eBioscience (antibody)

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This monoclonal targets CD5

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IgM Monoclonal Antibody (II/41), Biotin, eBioscience (antibody)

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CD19 Monoclonal Antibody (MB19-1), Biotin, eBioscience (antibody)

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This monoclonal targets CD19

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CD3e Monoclonal Antibody (145-2C11), Biotin, eBioscience (antibody)

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This monoclonal targets CD3e

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CD127 Monoclonal Antibody (A7R34), Biotin, eBioscience (antibody)

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This monoclonal targets CD127

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Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), Biotin, eBioscience (antibody)

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This monoclonal targets Ly-6G/Ly-6C

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TER-119 Monoclonal Antibody (TER-119), Biotin, eBioscience (antibody)

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CD45R (B220) Monoclonal Antibody (RA3-6B2), Biotin, Functional Grade, eBioscience (antibody)

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This monoclonal targets CD45R (B220)

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CD8a Monoclonal Antibody (53-6.7), Biotin, eBioscience (antibody)

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This monoclonal targets CD8a

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CD4 Monoclonal Antibody (GK1.5), Biotin, eBioscience (antibody)

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This monoclonal targets CD4

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Microsoft Excel (software resource)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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