Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1. Our dissection of the GMP hierarchy led us to further identify a previously unknown intermediate proNeu2 population. Similar populations could be detected in human samples. proNeu1s, but not proNeu2s, selectively expanded during the early phase of sepsis at the expense of monocytes. Collectively, our findings help shape the neutrophil maturation trajectory roadmap and challenge the current definition of GMPs.
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
We thank all members of L.G.N laboratory, the SIgN flow cytometry team, the SIgN functional genomics team for their assistance with transcriptomics and the SIgN mouse core facility for their technical help and support. This research was funded by SIgN core funding, A*STAR, Singapore. S.Z.C. is supported by Singapore Ministry of Health’s National Medical Research Council under its Open Fund - Young Investigator Research Grant (OFYIRG17may036). F.G. is an EMBO YIP awardee and is supported by Singapore Immunology Network (SIgN) core funding, as well as Singapore National Research Foundation Investigatorship (NRFI) (NRF2016NRF-NRFI001-02). L.G.N is supported by Singapore Immunology Network (SIgN) core funding. SIgN Flow Cytometry facility is supported by National Research Foundation (NRF) Singapore, under Shared Infrastructure Support (SIS) (NRF2017_SISFP09).