Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells.
MetadataShow full item record
Karamitros, D., Stoilova, B., Aboukhalil, Z., Hamey, F., Reinisch, A., Samitsch, M., Quek, L., et al. (2018). Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells.. Nature immunology, 19 (1), 85-97. https://doi.org/10.1038/s41590-017-0001-2
The human hemopoietic progenitor hierarchy producing lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations produce lymphoid and myeloid cells, but they remain incompletely characterized. Here, we demonstrate current cord blood lympho-myeloid containing progenitor populations - the lymphoid-primed multi-potential progenitor (LMPP), granulocyte-macrophage progenitor (GMP) and multi-lymphoid progenitor (MLP) - are functionally and transcriptionally distinct and heterogeneous at the clonal level, with progenitors of many different functional potentials present. Though most progenitors have uni-lineage myeloid or lymphoid potential, bi- and rarer multi-lineage progenitors occur in LMPP, GMP and MLP. This coupled with single cell expression analyses, suggests a continuum of progenitors execute lymphoid and myeloid differentiation rather than only uni-lineage progenitors being present downstream of stem cells.
Myeloid Progenitor Cells, Cells, Cultured, Animals, Humans, Mice, Hematopoietic Stem Cell Transplantation, Transplantation, Heterologous, Cell Separation, Gene Expression Profiling, Cell Differentiation, Hematopoiesis, Cell Lineage, Lymphoid Progenitor Cells, Single-Cell Analysis
MRC (MHU Award G1000729, MRC Disease Team Award 4050189188), CRUK (Program Grant to PV C7893/A12796, CRUK program grant to BG C1163/A21762), Bloodwise (Specialist Program 13001 and Project grant to 12019), an MRC PhD studentship (F.H. & Z.A.), The MRC Single Cell Award (MR/M00919X/1) to the WIMM and the Oxford Partnership Comprehensive Biomedical Research Centre (NIHR BRC Funding scheme). We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z) for generation of sequencing data. R.M. was supported by National Institutes of Health grants R01CA188055 and U01HL099999, New York Stem Cell Foundation Robertson Investigator and Leukemia and Lymphoma Society Scholar Award. A.R. was supported by an Erwin-Schroedinger Research fellowship from the Austrian Science Fund (FWF).
Cancer Research UK (21762)
Leukaemia & Lymphoma Research (12029)
Wellcome Trust (206328/Z/17/Z)
External DOI: https://doi.org/10.1038/s41590-017-0001-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/268137