Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

被引:174
作者
Drissen, Roy [1 ,2 ]
Buza-Vidas, Natalija [2 ]
Woll, Petter [1 ,3 ]
Thongjuea, Supat [1 ]
Gambardella, Adriana [1 ,2 ]
Giustacchini, Alice [1 ,3 ]
Mancini, Elena [4 ]
Zriwil, Alya [5 ]
Lutteropp, Michael [1 ,3 ]
Grover, Amit [1 ,2 ,4 ]
Mead, Adam [1 ,3 ]
Sitnicka, Ewa [5 ]
Jacobsen, Sten Eirik W. [1 ,3 ]
Nerlov, Claus [1 ,2 ,4 ]
机构
[1] Univ Oxford, Weatherall Inst Mol Med, MRC Mol Hematol Unit, Oxford, England
[2] Univ Edinburgh, Inst Stem Cell Res, Edinburgh, Midlothian, Scotland
[3] Univ Oxford, Weatherall Inst Mol Med, Haematopoiet Stem Cell Lab, Oxford, England
[4] EMBL Mouse Biol Program, Monterotondo, Italy
[5] Lund Univ, Div Mol Hematol, Lund, Sweden
基金
英国医学研究理事会; 英国工程与自然科学研究理事会; 英国惠康基金;
关键词
HEMATOPOIETIC STEM-CELLS; PRIMED MULTIPOTENT PROGENITORS; TRANSCRIPTION FACTOR GATA-1; MURINE FETAL LIVER; MOUSE BONE-MARROW; LINEAGE COMMITMENT; EOSINOPHIL LINEAGE; C/EBP-BETA; B-CELL; T-CELL;
D O I
10.1038/ni.3412
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)Fc gamma RII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.
引用
收藏
页码:666 / +
页数:13
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