Calzetti Federica, Finotti Giulia, Tamassia Nicola, Bianchetto-Aguilera Francisco, Castellucci Monica, Canè Stefania, Lonardi Silvia, Cavallini Chiara, Matte Alessandro, Gasperini Sara, Signoretto Ilaria, Benedetti Fabio, Bonifacio Massimiliano, Vermi William, Ugel Stefano, Bronte Vincenzo, Tecchio Cristina, Scapini Patrizia, Cassatella Marco A
Section of General Pathology, Department of Medicine, University of Verona, Verona, Italy.
Centro Piattaforme Tecnologiche, University of Verona, Verona, Italy.
Nat Immunol. 2022 May;23(5):679-691. doi: 10.1038/s41590-022-01189-z. Epub 2022 Apr 28.
Here we report the identification of human CD66bCD64CD115 neutrophil-committed progenitor cells (NCPs) within the SSCCD45CD34 and CD34 subsets in the bone marrow. NCPs were either CD45RA or CD45RA, and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b neutrophils in both in vitro differentiation and in vivo adoptive transfer experiments. Single-cell RNA-sequencing analysis indicated NCPs fell into four clusters, characterized by different maturation stages and distributed along two differentiation routes. One of the clusters was characterized by an interferon-stimulated gene signature, consistent with the reported expansion of peripheral mature neutrophil subsets that express interferon-stimulated genes in diseased individuals. Finally, comparison of transcriptomic and phenotypic profiles indicated NCPs represented earlier neutrophil precursors than the previously described early neutrophil progenitors (eNePs), proNeus and COVID-19 proNeus. Altogether, our data shed light on the very early phases of neutrophil ontogeny.
在此，我们报告了在骨髓的SSCCD45CD34和CD34亚群中鉴定出人类CD66bCD64CD115嗜中性粒细胞定向祖细胞（NCPs）。NCPs要么是CD45RA，要么是CD45RA，体外实验表明，获得CD45RA对于其成熟过程并非必需。在体外分化和体内过继转移实验中，NCPs专门生成人类CD66b嗜中性粒细胞。单细胞RNA测序分析表明，NCPs分为四个簇，其特征在于不同的成熟阶段，并沿两条分化途径分布。其中一个簇的特征是具有干扰素刺激基因特征，这与报道的在患病个体中表达干扰素刺激基因的外周成熟嗜中性粒细胞亚群的扩增一致。最后，转录组和表型谱的比较表明，NCPs代表的嗜中性粒细胞前体比先前描述的早期嗜中性粒细胞祖细胞（eNePs）、原嗜中性粒细胞和新冠原嗜中性粒细胞更早。总之，我们的数据揭示了嗜中性粒细胞个体发生的非常早期阶段。
