R-SPONDIN2 Mesenchymal Cells Form the Bud Tip Progenitor Niche During Human Lung Development

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2022 Jun 9

PMID 35679862

Authors

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

Affiliations

Soon will be listed here.

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.

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