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

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dc.contributor.coauthorHein, Renee F. C.
dc.contributor.coauthorWu, Joshua H.
dc.contributor.coauthorHolloway, Emily M.
dc.contributor.coauthorFrum, Tristan
dc.contributor.coauthorConchola, Ansley S.
dc.contributor.coauthorTsai, Yu-Hwai
dc.contributor.coauthorWu, Angeline
dc.contributor.coauthorFine, Alexis S.
dc.contributor.coauthorMiller, Alyssa J.
dc.contributor.coauthorSzenker-Ravi, Emmanuelle
dc.contributor.coauthorYan, Kelley S.
dc.contributor.coauthorKuo, Calvin J.
dc.contributor.coauthorGlass, Ian
dc.contributor.coauthorFrum, Tristan
dc.contributor.coauthorGlass, Ian
dc.contributor.coauthorSpence, Jason R.
dc.contributor.kuauthorReversade, Bruno
dc.contributor.kuprofileFaculty Member
dc.contributor.schoolcollegeinstituteSchool of Medicine
dc.date.accessioned2024-11-09T13:52:46Z
dc.date.issued2022
dc.description.abstractThe 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 theWNT 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.
dc.description.fulltextYES
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue13
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipThis project has been made possible in part by grant number CZF2019-002440 from the Chan Zuckerberg Initiative DAF, an advised fund from the Silicon Valley Community Foundation, and in part by the NIH-NHLBI (R01HL119215) funding to J.R.S.
dc.description.sponsorshipR.F.C.H. was supported by a NIH Tissue En- gineering and Regenerative Medicine Training Grant (NIH-NIDCR T32DE 007057) and by a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (NIH-NHLBI F31HL152531)
dc.description.sponsorshipA.J.M. was supported by a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (NIH- NHLBI F31HL142197)
dc.description.sponsorshipE.M.H. was supported by a Ruth L. Kirschstein Predoc- toral Individual National Research Service Award (NIH-NHBLI F31HL146162)
dc.description.sponsorshipT.F. was supported by a NIH Tissue Engineering and Regenerative Medicine Training Grant (NIH-NIDCR T32DE007057)
dc.description.sponsorshipA.S.C. was supported by the T32 Michigan Medical Scientist Training Program (5T32GM007863-40)
dc.description.sponsorshipI.G. and the University of Washington Laboratory of Developmental Biology was supported by NIH award number 5R24HD000836 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). B.R. is a fellow of the Branco Weiss Foundation (Switzerland) and the National Research Foundation (Singapore), and an A*STAR and EMBO Young Investi- gator. This work was supported by an inaugural Use-Inspired Basic Research (UIBR) central fund from the Agency for Science, Technology and Research (A*STAR) and National Medical Research Council Open Fund– Individual Research Grants (OF-YIRG,#OFYIRG18May-0053
dc.description.sponsorshipand OF-IRG, #OFIRG20- Nov-0057), to E.S.-R and B.R., respectively. We would like to thank Judy Opp and the University of Michigan Advanced Genomics core for the operation of the 103 chromium single-cell capture plat- form, the University of Michigan Microscopy core for providing access to confocal microscopes, the Flow Cytometry core for providing access to flow cytometers, and the Vector core for providing lentivirus production and adeno- virus purification and expansion services. We would also like to thank the Uni- versity of Washington Laboratory of Developmental Biology. Lastly, we would like to thank Michael Dame and the Translational Tissue Modeling Laboratory (TTML) for providing helpful suggestions regarding the use of WNT3a afamin conditioned media as well as Lindy K. Brastrom for her careful technical editing of the manuscript.
dc.description.versionPublisher version
dc.description.volume57
dc.formatpdf
dc.identifier.doi10.1016/j.devcel.2022.05.010
dc.identifier.eissn1878-1551
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR03800
dc.identifier.issn1534-5807
dc.identifier.linkhttps://doi.org/10.1016/j.devcel.2022.05.010
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85133539208
dc.identifier.urihttps://hdl.handle.net/20.500.14288/3993
dc.identifier.wos830060000006
dc.keywordsBud tip progenitor
dc.keywordsHuman development
dc.keywordsLung development
dc.keywordsLung mesenchyme
dc.keywordsLung organoid
dc.keywordsMesenchymal cell
dc.keywordsR-Spondin2
dc.keywordsRSPO2
dc.keywordsSingle-cell RNA-seq
dc.keywordsStem cell niche
dc.languageEnglish
dc.publisherElsevier
dc.relation.grantnoNA
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/10652
dc.sourceDevelopmental Cell
dc.subjectCell biology
dc.subjectDevelopmental biology
dc.titleR-SPONDIN2(+) mesenchymal cells form the bud tip progenitor niche during human lung development
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorReversade, Bruno

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