Publication:
NLRP7 plays a functional role in regulating BMP4 signaling during differentiation of patient-derived trophoblasts

dc.contributor.coauthorAlici-Garipcan, Aybüke
dc.contributor.coauthorSuder, İlke
dc.contributor.coauthorÜlker, Volkan
dc.contributor.coauthorÖzören, Nesrin
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorÖnder, Tamer Tevfik
dc.contributor.kuauthorÖzçimen, Burcu
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T12:11:13Z
dc.date.issued2020
dc.description.abstractComplete hydatidiform mole (HM) is a gestational trophoblastic disease resulting in hyperproliferation of trophoblast cells and absence of embryo development. Mutations in the maternal-effect gene NLRP7 are the major cause of familial recurrent complete HM. Here, we established an in vitro model of HM using patient-specific induced pluripotent stem cells (iPSCs) derived trophoblasts harboring NLRP7 mutations. Using whole transcriptome profiling during trophoblast differentiation, we showed that impaired NLRP7 expression results in precocious downregulation of pluripotency factors, activation of trophoblast lineage markers, and promotes maturation of differentiated extraembryonic cell types such as syncytiotrophoblasts. Interestingly, we found that these phenotypes are dependent on BMP4 signaling and BMP pathway inhibition corrected the excessive trophoblast differentiation of patient-derived iPSCs. Our human iPSC model of a genetic placental disease recapitulates aspects of trophoblast biology, highlights the broad utility of iPSC-derived trophoblasts for modeling human placental diseases and identifies NLRP7 as an essential modulator of key developmental cell fate regulators.
dc.description.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TÜBİTAK)
dc.description.sponsorshipBoğaziçi University Research Funding Office
dc.description.sponsorshipEMBO Installation Grant
dc.description.versionPublisher version
dc.description.volume11
dc.identifier.doi10.1038/s41419-020-02884-1
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR02370
dc.identifier.issn2041-4889
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85089598145
dc.identifier.urihttps://doi.org/10.1038/s41419-020-02884-1
dc.identifier.wos566241700003
dc.keywordsPluripotent stem-cells
dc.keywordsRecurrent hydatidiform moles
dc.keywordsBMP4-driven differentiation
dc.keywordsIn-vitro
dc.keywordsMutations
dc.keywordsExpression
dc.keywordsYY1
dc.keywordsRecognition
dc.keywordsVariant
dc.language.isoeng
dc.publisherSpringer Nature
dc.relation.grantnoSBAG-112S115, KBAG217z131
dc.relation.grantnoBAP:7360
dc.relation.ispartofCell Death and Disease
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/9006
dc.subjectCell biology
dc.titleNLRP7 plays a functional role in regulating BMP4 signaling during differentiation of patient-derived trophoblasts
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorÖnder, Tamer Tevfik
local.contributor.kuauthorÖzçimen, Burcu
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
relation.isOrgUnitOfPublicationd02929e1-2a70-44f0-ae17-7819f587bedd
relation.isOrgUnitOfPublication.latestForDiscoveryd02929e1-2a70-44f0-ae17-7819f587bedd
relation.isParentOrgUnitOfPublication17f2dc8e-6e54-4fa8-b5e0-d6415123a93e
relation.isParentOrgUnitOfPublication.latestForDiscovery17f2dc8e-6e54-4fa8-b5e0-d6415123a93e

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
9006.pdf
Size:
2.64 MB
Format:
Adobe Portable Document Format