| Literature DB >> 35679862 |
Renee F C Hein1, Joshua H Wu2, Emily M Holloway1, Tristan Frum2, Ansley S Conchola3, Yu-Hwai Tsai2, Angeline Wu2, Alexis S Fine2, Alyssa J Miller3, Emmanuelle Szenker-Ravi4, Kelley S Yan5, Calvin J Kuo6, Ian Glass7, Bruno Reversade8, Jason R Spence9.
Abstract
The human respiratory epithelium is derived from a progenitor cell in the distal buds of the developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function in the developing human lung are poorly understood. We interrogated single-cell RNA sequencing data from multiple human lung specimens and identified a mesenchymal cell population present during development that is highly enriched for expression of the WNT agonist RSPO2, and we found that the adjacent bud tip progenitors are enriched for the RSPO2 receptor LGR5. Functional experiments using organoid models, explant cultures, and FACS-isolated RSPO2+ mesenchyme show that RSPO2 is a critical niche cue that potentiates WNT signaling in bud tip progenitors to support their maintenance and multipotency.Entities:
Keywords: R-Spondin2; RSPO2; bud tip progenitor; human development; lung development; lung mesenchyme; lung organoid; mesenchymal cell; single-cell RNA-seq; stem cell niche
Mesh：
Year: 2022 PMID： 35679862 PMCID： PMC9283295 DOI： 10.1016/j.devcel.2022.05.010
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 13.417