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

Summary, in English

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(-)FcγRII/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.

• Author: Roy Drissen; Natalija Buza-Vidas; Petter Woll; Supat Thongjuea; Adriana Gambardella; Alice Giustacchini; Elena Mancini; Alya Zriwil; Michael Lutteropp; Amit Grover; Adam Mead; Ewa Sitnicka; Sten Eirik W Jacobsen; Claus Nerlov
• Department/s: Division of Molecular Hematology (DMH); StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2016-06
• Language: English
• Pages: 666-676
• Publication/Series: Nature Immunology
• Volume: 17
• Issue: 6
• Links: http://dx.doi.org/10.1038/ni.3412
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Immunology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1529-2908