期刊
NATURE IMMUNOLOGY
卷 17, 期 6, 页码 666-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3412
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资金
- Wellcome Trust Equipment Grant [WT087371MA]
- WIMM
- Medical Research Council Grants [MC_UU_12009, MC_UU_12025, G0902418]
- Association for International Cancer Research [11-0724]
- Medical Research Council (UK Program Grant) [G0801073, MC_UU_12009/5]
- European Commission FP7 (CardioCell project)
- European Commission FP7 (EuroSyStem project)
- [G0701761]
- [G0900892]
- [MC_UU_12009/7]
- EPSRC [EP/H018921/1] Funding Source: UKRI
- MRC [MC_UU_12009/7, G0900892, G0801073, G0701761, MC_PC_12020, MC_UU_12009/16, MR/L006340/1, MR/M00919X/1, G0501838, MR/L012766/1, MC_UU_12009/5] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [1104521, EP/H018921/1] Funding Source: researchfish
- Medical Research Council [G0701761, MC_UU_12009/16, MR/L006340/1, MR/L012766/1, MC_UU_12009/5, MR/M00919X/1, MC_PC_12020, G0900892, G0501838, MC_UU_12009/7, G0801073] Funding Source: researchfish
- Worldwide Cancer Research [11-0724] Funding Source: researchfish
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.
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