Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Developmental cell, 2022-07, Vol.57 (13), p.1598-1614.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •scRNA-seq of developing human distal lung mesenchyme identified cellular heterogeneity•RSPO2+ mesenchymal cells lie adjacent to LGR5+ epithelial bud tip progenitors•Blocking RSPO2/LGR5 in vitro reduced WNT signaling and led to airway differentiation•RSPO2+ mesenchyme provides a niche for bud tips in co-cultures Hein et al. present the scRNA-seq of the developing human distal lung, showing transcriptionally distinct populations of mesenchyme. Spatial profiling showed that RSPO2+ mesenchymal cells are physically adjacent to LGR5+ epithelial bud tips. Organoid experiments revealed that RSPO2+ cells create a high WNT signaling environment, supporting bud tip identity and multipotency.