意大利维罗纳大学Marco A. Cassatella课题组发现，人类骨髓中的CD66b^-CD64^dimCD115^-细胞代表中性粒细胞的前体。这一研究成果于2022年4月28日在线发表在国际学术期刊《自然—免疫学》上。

研究人员在骨髓中SSC^loCD45^dimCD34⁺和CD34^dim/-亚群中鉴定了人类CD66b^-CD64^dimCD115^-中性粒细胞祖细胞（NCP）。NCP要么是CD45RA⁺，要么是CD45RA^-，体外实验表明，CD45RA的获得对其成熟过程不是强制性的。在体外分化和体内过继转移实验中，NCP专门生成人CD66b⁺的中性粒细胞。单细胞RNA测序分析表明，NCP分为四个集群，以不同的成熟阶段为特征，沿着两条分化路线分布。

其中一个集群的特点是有干扰素刺激的基因特征，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中性粒细胞亚群的扩增相一致。最后，转录组和表型特征的比较表明，NCP是比以前描述的早期中性粒细胞前体（eNeP）、proNeus和COVID-19 proNeus更早的中性粒细胞前体。总的来说，这些数据揭示了中性粒细胞本体发育的非常早期阶段。

附：英文原文

Title: CD66b−CD64dimCD115− cells in the human bone marrow represent neutrophil-committed progenitors

Author: Calzetti, Federica, Finotti, Giulia, Tamassia, Nicola, Bianchetto-Aguilera, Francisco, Castellucci, Monica, Can, 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.

Issue&Volume: 2022-04-28

Abstract: Here we report the identification of human CD66bCD64dimCD115 neutrophil-committed progenitor cells (NCPs) within the SSCloCD45dimCD34+ and CD34dim/ 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.

DOI: 10.1038/s41590-022-01189-z

Source: https://www.nature.com/articles/s41590-022-01189-z