Identification and characterization of human CD34+ and CD34dim/- neutrophil-committed progenitors

Calzetti, Federica; Finotti, Giulia; Tamassia, Nicola; Bianchetto-Aguilera, Francisco; Castellucci, Monica; Cavallini, Chiara; Mattè, Alessandro; Gasperini, Sara; Benedetti, Fabio; Bonifacio, Massimiliano; Tecchio, Cristina; Scapini, Patrizia; Cassatella, Marco A.

We report the identification of human CD66b−CD64dimCD115− neutrophil-committed progenitors within SSClowCD45dimCD34+ and CD34dim/− bone marrow cells, that we named neutrophil myeloblast (NMs). CD34+ and CD34dim/−NMs resulted as either CD45RA+ or CD45RA−, with CD34+CD45RA−NMs found as selectively expanded in chronic-phase chronic myeloid leukemia patients. By scRNA-seq experiments, CD34+ and CD34dim/−NMs were found to consist of combinations of four cell clusters, characterized by different maturation stages and distributed along two differentiation routes. Cell clusters were identified by neutrophil-specific gene profiles, one of them associated to an interferon-stimulated gene (ISG) signature, hence supporting recently identified expansions of mature neutrophil subsets expressing ISGs in blood of diseased individuals. Altogether, our data shed light on the very early phases of neutrophil ontogeny.