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Single cell RNA sequencing reveals molecular and functional platelet bias of aged hematopoietic stem cells

Abstract:
Aged hematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared to young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Analyzing HSC transcriptomes and HSC function at the single cell level we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor was accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis
Publication status:
Published
Peer review status:
Peer reviewed

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More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author


More from this funder
Funding agency for:
Nerlov, C
Jacobsen, S
Grant:
MC_UU_12009/7
H4RPLK0
More from this funder
Funding agency for:
Nerlov, C
Jacobsen, S
Grant:
MC_UU_12009/7
H4RPLK0
MC_UU_12009; MC_UU_12025; G0902418; G0701761; G0900892
More from this funder
Funding agency for:
Nerlov, C
Grant:
MC_UU_12009/7


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Publication date:
2016-03-24
Acceptance date:
2016-02-18
ISSN:
2041-1723


Pubs id:
pubs:605440
UUID:
uuid:75891742-4110-4201-948a-59f1a868d8a9
Local pid:
pubs:605440
Source identifiers:
605440
Deposit date:
2016-02-20
ARK identifier:

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