Early human lung immune cell development and its role in epithelial cell fate

• DOI: 10.1101/2022.12.13.519713
• Publication Date: 2022-12-15T20:30:24Z
• Authors: Josephine L. Barnes; Peng He; Masahiro Yoshida; Kaylee B. Worlock; Rik G.H. Lindeboom; Chenqu Suo; J. Patrick Pett; Anna Wilbrey-Clark; Emma Dann; Lira Mamanova; Laura Richardson; Amanda J. Oliver; Adam Pennycuick; Jessica Allen-Hyt...; Iván T. Herczeg; Robert E. Hynds; Vitor H. Teixeira; Muzlifah Haniffa; Kyungtae Lim; Dawei Sun; Emma L. Rawlins; Krzysztof Polanski; Paul A. Lyons; John C. Marioni; Zewen Kelvin Tuong; Menna R. Clatworthy; James L. Reading; Sam M. Janes; Sarah A. Teichmann; Kerstin B. Meyer; Marko Z. Nikolić
• Keywords: Pediatric; 0301 basic medicine; 1.1 Normal biological development and functioning; Inflammatory and immune system; 32 Biomedical and Clinical Sciences; Perinatal Period - Conditions Originating in Perinatal Period; FOS: Health sciences; Stem Cell Research; 3. Good health; 3204 Immunology; 03 medical and health sciences; Infectious Diseases; Emerging Infectious Diseases; Biodefense; 2.1 Biological and endogenous factors; Stem Cell Research - Nonembryonic - Non-Human; Lung

Abstract During human development, lungs develop their roles of gas exchange and barrier function. Recent single cell studies have focused on epithelial mesenchymal types, but much less is known about the developing lung immune cells, although airways are a major site mucosal immunity after birth. An open question whether tissue-resident cells play role in shaping tissue as it develops utero . In order to address this, we profiled using scRNAseq, smFISH immunohistochemistry. At embryonic stage, observed an early wave innate including ILCs, NK, myeloid lineage progenitors. By canalicular detected naive T lymphocytes high cytotoxicity genes, mature B lymphocytes, B1 cells. Our analysis suggests that fetal provide niche for full maturation. Given abundance investigated possible effect maturation found IL-1β drives progenitor exit from self-renewal differentiation basal vitro vivo , IL-1β-producing were adjacent tips, suggesting may direct epithelium.