Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.
复制标题
DOI：
10.1038/ncomms11075
复制
发表时间：
2016-03-24
影响因子：
16.6
通讯作者：
Nerlov C
中科院分区：
文献类型：
--
作者：
Grover A;Sanjuan-Pla A;Thongjuea S;Carrelha J;Giustacchini A;Gambardella A;Macaulay I;Mancini E;Luis TC;Mead A;Jacobsen SE;Nerlov C
与年轻的造血干细胞相比，老年造血干细胞（HSC）产生更多的髓样细胞和更少的淋巴样细胞，导致老年个体的适应性免疫力下降。然而，目前尚不清楚HSC的内在变化和偏向HSC亚群之间平衡的变化如何各自促成改变的谱系输出。在这里，通过在单细胞水平上分析HSC转录组和HSC功能，我们确定分子血小板启动和功能性血小板偏向性增加是HSC的主要年龄依赖性变化，包括以前未识别的一类专门产生血小板的HSC的显着增加。通过FOG-1转录因子的损失而导致的HSC血小板编程的消耗伴随着淋巴输出的增加。因此，血小板偏倚增加可能导致与年龄相关的淋巴细胞生成减少。 随着年龄的增长，造血干细胞（HSC）产生的髓样细胞比淋巴样细胞多，影响了适应性免疫。通过将HSC单细胞转录组学与功能研究相结合，Grover等人发现，老年鼠HSC中的血小板生成也增加，并表明FOG-1转录因子有助于年龄依赖性血小板偏倚。
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. With age, haematopoietic stem cells (HSCs) produce more myeloid than lymphoid cells, affecting adaptive immunity. By combining HSC single cell transcriptomics with functional studies, Grover et al. find that platelet production is also increased in old murine HSCs and show that the FOG-1 transcription factor contributes to the age-dependent platelet bias.