@article{7f5cfd19aede4814906622f7ba4256ac,
title = "Coexpression of CD71 and CD117 Identifies an Early Unipotent Neutrophil Progenitor Population in Human Bone Marrow",
abstract = "Neutrophils are the most abundant peripheral immune cells and thus, are continually replenished by bone marrow-derived progenitors. Still, how newly identified neutrophil subsets fit into the bone marrow neutrophil lineage remains unclear. Here, we use mass cytometry to show that two recently defined human neutrophil progenitor populations contain a homogeneous progenitor subset we term “early neutrophil progenitors” (eNePs) (Lin−CD66b+CD117+CD71+). Surface marker- and RNA-expression analyses, together with in vitro colony formation and in vivo adoptive humanized mouse transfers, indicate that eNePs are the earliest human neutrophil progenitors. Furthermore, we identified CD71 as a marker associated with the earliest neutrophil developmental stages. Expression of CD71 marks proliferating neutrophils, which were expanded in the blood of melanoma patients and detectable in blood and tumors from lung cancer patients. In summary, we establish CD117+CD71+ eNeP as the inceptive human neutrophil progenitor and propose a refined model of the neutrophil developmental lineage in bone marrow.",
keywords = "CD71, bone marrow, cancer, neutrophil development, neutrophil progenitors, neutrophils, promyelocytes",
author = "Dinh, {Huy Q.} and Tobias Eggert and Meyer, {Melissa A.} and Zhu, {Yanfang Peipei} and Olingy, {Claire E.} and Ryan Llewellyn and Runpei Wu and Hedrick, {Catherine C.}",
note = "Funding Information: We thank Daniel Araujo for critical editing and helpful discussions. Sequencing data were generated from a grant supported by the Tullie and Rickey Families{\textquoteright} SPARK Awards program at La Jolla Institute (LJI) for Immunology to H.Q.D. M.A.M acknowledges support from the National Institutes of Health ( 2T32AR064194 ). This work was supported by NIH grants U01 CA224766 , R01 CA202987 , R01 HL134236 , and P01 HL136275 (all to C.C.H.). We would like to thank the LJI Flow Cytometry Core Facility for assistance with cell sorting. The FACSAria-3 cell sorter and the Fluidigm CyTOF Helios were acquired through the NIH Shared Instrumentation Grant (SIG) Program S10 (FACSAria II Cell Sorter S10 RR027366 and CyTOF Mass Cytometer S10 OD018499 to LJI). Funding Information: We thank Daniel Araujo for critical editing and helpful discussions. Sequencing data were generated from a grant supported by the Tullie and Rickey Families? SPARK Awards program at La Jolla Institute (LJI) for Immunology to H.Q.D. M.A.M acknowledges support from the National Institutes of Health (2T32AR064194). This work was supported by NIH grants U01 CA224766, R01 CA202987, R01 HL134236, and P01 HL136275 (all to C.C.H.). We would like to thank the LJI Flow Cytometry Core Facility for assistance with cell sorting. The FACSAria-3 cell sorter and the Fluidigm CyTOF Helios were acquired through the NIH Shared Instrumentation Grant (SIG) Program S10 (FACSAria II Cell Sorter S10 RR027366 and CyTOF Mass Cytometer S10 OD018499 to LJI). H.Q.D, T.E. and C.C.H. conceptualized the project. H.Q.D. T.E. and C.E.O. analyzed CyTOF and RNA-seq data. Y.P.Z. designed the CyTOF panel. T.E. Y.P.Z. R.L. M.A.M. R.W. performed CyTOF and flow cytometry experiments. T.E. prepared samples for RNA-seq, analyzed flow cytometry data, and performed and analyzed Methocult experiments. M.A.M. performed the NSG-SGM3 adoptive transfer experiments and analyzed the data. H.Q.D. and T.E. drafted the original figures and manuscript with significant contributions from M.A.M. and C.E.O. All authors reviewed and edited the manuscripts. C.C.H. and H.Q.D. acquired funding and supervised the project. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = aug,
day = "18",
doi = "10.1016/j.immuni.2020.07.017",
language = "English (US)",
volume = "53",
pages = "319--334.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}