R-SPONDIN2+ mesenchymal cells form the bud tip progenitor niche during human lung development

Renee F.C. Hein, Joshua H. Wu, Emily M. Holloway, Tristan Frum, Ansley S. Conchola, Yu Hwai Tsai, Angeline Wu, Alexis S. Fine, Alyssa J. Miller, Emmanuelle Szenker-Ravi, Kelley S. Yan, Calvin J. Kuo, Ian Glass, Bruno Reversade, Jason R. Spence

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)1598-1614.e8
JournalDevelopmental Cell
Issue number13
StatePublished - Jul 11 2022
Externally publishedYes

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Generated from Scopus record by KAUST IRTS on 2023-02-15


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