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

被引：244

作者：

Grover, Amit ^{[1
,2
]}

Sanjuan-Pla, Alejandra ^{[1
,2
]}

Thongjuea, Supat ^{[1
]}

Carrelha, Joana ^{[1
,3
]}

Giustacchini, Alice ^{[1
,3
]}

Gambardella, Adriana ^{[1
,2
,4
]}

Macaulay, Iain ^{[1
,3
]}

Mancini, Elena ^{[4
]}

Luis, Tiago C. ^{[1
,3
]}

Mead, Adam ^{[1
,3
]}

Jacobsen, Sten Eirik W. ^{[1
,3
]}

Nerlov, Claus ^{[1
,2
,4
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford OX3 9DS, England

[2] Univ Edinburgh, Inst Stem Cell Res, Edinburgh EH16 4UU, Midlothian, Scotland

[3] Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Lab, Oxford OX3 9DS, England

[4] EMBL Mouse Biol Program, I-00015 Monterotondo, Italy

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

PROGENITOR CELLS; PROLIFERATION; IDENTIFICATION; COMPARTMENT; MECHANISM; FREQUENCY; DEFECTS;

D O I：

10.1038/ncomms11075

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with 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. Here, by analysing 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 is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis.

引用

页数：12

共 42 条

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