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

doi:10.1016/j.devcel.2022.05.010

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 journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1598-1614.e8
Journal	Developmental Cell
Volume	57
Issue number	13
DOIs	https://doi.org/10.1016/j.devcel.2022.05.010
State	Published - Jul 11 2022
Externally published	Yes

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

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Hein, R. F. C., Wu, J. H., Holloway, E. M., Frum, T., Conchola, A. S., Tsai, Y. H., Wu, A., Fine, A. S., Miller, A. J., Szenker-Ravi, E., Yan, K. S., Kuo, C. J., Glass, I., Reversade, B., & Spence, J. R. (2022). R-SPONDIN2+ mesenchymal cells form the bud tip progenitor niche during human lung development. Developmental Cell, 57(13), 1598-1614.e8. https://doi.org/10.1016/j.devcel.2022.05.010

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

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.",

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

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doi = "10.1016/j.devcel.2022.05.010",

language = "English (US)",

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T1 - R-SPONDIN2+ mesenchymal cells form the bud tip progenitor niche during human lung development

AU - Hein, Renee F.C.

AU - Wu, Joshua H.

AU - Holloway, Emily M.

AU - Frum, Tristan

AU - Conchola, Ansley S.

AU - Tsai, Yu Hwai

AU - Wu, Angeline

AU - Fine, Alexis S.

AU - Miller, Alyssa J.

AU - Szenker-Ravi, Emmanuelle

AU - Yan, Kelley S.

AU - Kuo, Calvin J.

AU - Glass, Ian

AU - Reversade, Bruno

AU - Spence, Jason R.

N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15

PY - 2022/7/11

Y1 - 2022/7/11

N2 - 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.

AB - 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.

UR - https://linkinghub.elsevier.com/retrieve/pii/S1534580722003677

UR - http://www.scopus.com/inward/record.url?scp=85133539208&partnerID=8YFLogxK

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DO - 10.1016/j.devcel.2022.05.010

M3 - Article

C2 - 35679862

SN - 1534-5807

VL - 57

SP - 1598-1614.e8

JO - Developmental Cell

JF - Developmental Cell

IS - 13

ER -

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

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