Combinatorial Single-Cell Analyses of Granulocyte-Monocyte Progenitor Heterogeneity Reveals an Early Uni-potent Neutrophil Progenitor

Immanuel Kwok, Etienne Becht, Yu Xia, Melissa Ng, Ye Chean Teh, Leonard Tan, Maximilien Evrard, Jackson L.Y. Li, Hoa T.N. Tran, Yingrou Tan, Dehua Liu, Archita Mishra, Ka Hang Liong, Keith Leong, Yuning Zhang, Andre Olsson, Chinmay Kumar Mantri, Pavithra Shyamsunder, Zhaoyuan Liu, Cecile PiotCharles Antoine Dutertre, Hui Cheng, Sudipto Bari, Nicholas Ang, Subhra K. Biswas, H. Philip Koeffler, Hong Liang Tey, Anis Larbi, I. Hsin Su, Bernett Lee, Ashley St. John, Jerry K.Y. Chan, William Y.K. Hwang, Jinmiao Chen, Nathan Salomonis, Shu Zhen Chong, H. Leighton Grimes, Bing Liu, Andrés Hidalgo, Evan W. Newell, Tao Cheng, Florent Ginhoux, Lai Guan Ng

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

147 Citations (Scopus)

Résumé

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.

langue originaleAnglais
Pages (de - à)303-318.e5
journalImmunity
Volume53
Numéro de publication2
Les DOIs
étatPublié - 18 août 2020
Modification externeOui

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