Karamitros Dimitris, Stoilova Bilyana, Aboukhalil Zahra, Hamey Fiona, Reinisch Andreas, Samitsch Marina, Quek Lynn, Otto Georg, Repapi Emmanouela, Doondeea Jessica, Usukhbayar Batchimeg, Calvo Julien, Taylor Stephen, Goardon Nicolas, Six Emmanuelle, Pflumio Francoise, Porcher Catherine, Majeti Ravindra, Göttgens Berthold, Vyas Paresh
MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Nat Immunol. 2018 Jan;19(1):85-97. doi: 10.1038/s41590-017-0001-2. Epub 2017 Nov 21.
The hierarchy of human hemopoietic progenitor cells that produce lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations produce lymphoid and myeloid cells, but they remain incompletely characterized. Here we demonstrated that lympho-myeloid progenitor populations in cord blood - lymphoid-primed multi-potential progenitors (LMPPs), granulocyte-macrophage progenitors (GMPs) and multi-lymphoid progenitors (MLPs) - were functionally and transcriptionally distinct and heterogeneous at the clonal level, with progenitors of many different functional potentials present. Although most progenitors had the potential to develop into only one mature cell type ('uni-lineage potential'), bi- and rarer multi-lineage progenitors were present among LMPPs, GMPs and MLPs. Those findings, coupled with single-cell expression analyses, suggest that a continuum of progenitors execute lymphoid and myeloid differentiation, rather than only uni-lineage progenitors' being present downstream of stem cells.
产生淋巴细胞系和粒细胞 - 单核细胞(髓细胞)系的人类造血祖细胞层级尚不清楚。多个祖细胞群体可产生淋巴细胞和髓细胞,但它们的特征仍未完全明确。在此,我们证明了脐带血中的淋巴 - 髓细胞祖细胞群体——淋巴细胞启动的多能祖细胞(LMPP)、粒细胞 - 巨噬细胞祖细胞(GMP)和多淋巴细胞祖细胞(MLP)——在克隆水平上功能和转录上是不同且异质的,存在许多具有不同功能潜能的祖细胞。虽然大多数祖细胞仅具有发育成一种成熟细胞类型的潜能(“单谱系潜能”),但在LMPP、GMP和MLP中存在双谱系及更罕见的多谱系祖细胞。这些发现,再加上单细胞表达分析,表明祖细胞连续体执行淋巴细胞和髓细胞分化,而不仅仅是干细胞下游仅存在单谱系祖细胞。