4.7 Article

Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells

Journal

NATURE IMMUNOLOGY
Volume 19, Issue 1, Pages 85-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-017-0001-2

Keywords

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Categories

Funding

  1. Wellcome Trust [090532/Z/09/Z]
  2. MRC (MHU) [G1000729]
  3. MRC (MRC Disease Team Award) [4050189188]
  4. MRC (PhD studentship)
  5. MRC (Single Cell Award) [MR/M00919X/1]
  6. CRUK [C7893/A12796, C1163/A21762, CRUKDF0176-DK, C5255/A20758]
  7. Bloodwise [13001, 12019]
  8. Oxford Partnership Comprehensive Biomedical Research Centre (NIHR BRC Funding scheme)
  9. US National Institutes of Health [R01CA188055, U01HL099999]
  10. New York Stem Cell Foundation
  11. Leukemia and Lymphoma Society
  12. Austrian Science Fund (FWF)
  13. Austrian Science Fund (FWF) [J 3358] Funding Source: researchfish
  14. Medical Research Council [1581868, MC_PC_12009, MR/M00919X/1, G1000729, G1000801c, MC_UU_12009/11, 1514301, MC_U137961145, MC_UU_00016/9, MR/L008963/1, 1779543, MC_UU_12009/9] Funding Source: researchfish
  15. National Institute for Health Research [NF-SI-0617-10056] Funding Source: researchfish
  16. NATIONAL CANCER INSTITUTE [R01CA188055] Funding Source: NIH RePORTER
  17. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL099999] Funding Source: NIH RePORTER
  18. MRC [MC_UU_12009/11, MC_UU_00016/9, MC_UU_12009/9, G1000729, MR/L008963/1, MR/M00919X/1, MC_U137961145] Funding Source: UKRI

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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.

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