000270812 001__ 270812
000270812 005__ 20250127091658.0
000270812 0247_ $$2pmc$$apmc:PMC11552497
000270812 0247_ $$2doi$$a10.1242/dmm.050740
000270812 0247_ $$2pmid$$apmid:39034883
000270812 0247_ $$2ISSN$$a1754-8403
000270812 0247_ $$2ISSN$$a1754-8411
000270812 037__ $$aDZNE-2024-00902
000270812 041__ $$aEnglish
000270812 082__ $$a570
000270812 1001_ $$00000-0002-7557-8523$$aKagermeier, Theresa$$b0
000270812 245__ $$aHuman organoid model of pontocerebellar hypoplasia 2a recapitulates brain region-specific size differences.
000270812 260__ $$aCambridge$$bCompany of Biologists Limited$$c2024
000270812 3367_ $$2DRIVER$$aarticle
000270812 3367_ $$2DataCite$$aOutput Types/Journal article
000270812 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1722417253_4038
000270812 3367_ $$2BibTeX$$aARTICLE
000270812 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000270812 3367_ $$00$$2EndNote$$aJournal Article
000270812 520__ $$aPontocerebellar hypoplasia type 2a (PCH2a) is an ultra-rare, autosomal recessive pediatric disorder with limited treatment options. Its anatomical hallmark is hypoplasia of the cerebellum and pons accompanied by progressive microcephaly. A homozygous founder variant in TSEN54, which encodes a tRNA splicing endonuclease (TSEN) complex subunit, is causal. The pathological mechanism of PCH2a remains unknown due to the lack of a model system. Therefore, we developed human models of PCH2a using regionalized neural organoids. We generated induced pluripotent stem cell (iPSC) lines from three males with genetically confirmed PCH2a and subsequently differentiated cerebellar and neocortical organoids. Mirroring clinical neuroimaging findings, PCH2a cerebellar organoids were reduced in size compared to controls starting early in differentiation. Neocortical PCH2a organoids demonstrated milder growth deficits. Although PCH2a cerebellar organoids did not upregulate apoptosis, their stem cell zones showed altered proliferation kinetics, with increased proliferation at day 30 and reduced proliferation at day 50 compared to controls. In summary, we generated a human model of PCH2a, providing the foundation for deciphering brain region-specific disease mechanisms. Our first analyses suggest a neurodevelopmental aspect of PCH2a.
000270812 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000270812 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000270812 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000270812 650_7 $$2Other$$aApoptosis
000270812 650_7 $$2Other$$aCerebellum
000270812 650_7 $$2Other$$aDifferentiation
000270812 650_7 $$2Other$$aOrganoid
000270812 650_7 $$2Other$$aPCH2a
000270812 650_7 $$2Other$$aRare disease
000270812 650_2 $$2MeSH$$aHumans
000270812 650_2 $$2MeSH$$aOrganoids: pathology
000270812 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism
000270812 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: pathology
000270812 650_2 $$2MeSH$$aMale
000270812 650_2 $$2MeSH$$aBrain: pathology
000270812 650_2 $$2MeSH$$aCell Differentiation
000270812 650_2 $$2MeSH$$aCerebellum: abnormalities
000270812 650_2 $$2MeSH$$aCerebellum: pathology
000270812 650_2 $$2MeSH$$aOlivopontocerebellar Atrophies: pathology
000270812 650_2 $$2MeSH$$aOlivopontocerebellar Atrophies: genetics
000270812 650_2 $$2MeSH$$aCell Proliferation
000270812 650_2 $$2MeSH$$aOrgan Size
000270812 650_2 $$2MeSH$$aModels, Biological
000270812 650_2 $$2MeSH$$aApoptosis
000270812 650_2 $$2MeSH$$aCerebellar Diseases
000270812 7001_ $$0P:(DE-2719)2810998$$aHauser, Stefan$$b1
000270812 7001_ $$00000-0002-0579-6090$$aSarieva, Kseniia$$b2
000270812 7001_ $$00000-0003-2506-1961$$aLaugwitz, Lucia$$b3
000270812 7001_ $$00000-0002-2706-7163$$aGroeschel, Samuel$$b4
000270812 7001_ $$00000-0002-3651-1385$$aJanzarik, Wibke G$$b5
000270812 7001_ $$00000-0002-4832-9927$$aYentür, Zeynep$$b6
000270812 7001_ $$00000-0002-6479-3762$$aBecker, Katharina$$b7
000270812 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b8
000270812 7001_ $$0P:(DE-2719)9000936$$aKragelöh-Mann, Ingeborg$$b9
000270812 7001_ $$00000-0002-6381-2474$$aMayer, Simone$$b10
000270812 773__ $$0PERI:(DE-600)2451104-3$$a10.1242/dmm.050740$$gVol. 17, no. 7, p. dmm050740$$n7$$pdmm050740$$tDisease models & mechanisms$$v17$$x1754-8403$$y2024
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP1.xlsx
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP2.xlsx
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP3.xlsx
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP4Info.pdf
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%2BData.pdf$$yOpenAccess
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP1.csv
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP1.ods
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP1.xls
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP2.csv
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP2.ods
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP2.xls
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP3.csv
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP3.ods
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP3.xls
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%20SUP4Info.pdf?subformat=pdfa$$xpdfa
000270812 8564_ $$uhttps://pub.dzne.de/record/270812/files/DZNE-2024-00902%2BData.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000270812 909CO $$ooai:pub.dzne.de:270812$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000270812 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810998$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE
000270812 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810795$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000270812 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000270812 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x1
000270812 9141_ $$y2024
000270812 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-08-22
000270812 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000270812 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bDIS MODEL MECH : 2022$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-05-14T15:05:40Z
000270812 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-05-14T15:05:40Z
000270812 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000270812 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2021-05-14T15:05:40Z
000270812 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-22
000270812 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-22
000270812 9201_ $$0I:(DE-2719)5000005$$kAG Schöls$$lClinical Neurogenetics$$x0
000270812 9201_ $$0I:(DE-2719)1210016$$kAG Hauser$$lAdvanced cellular models of neurodegeneration$$x1
000270812 980__ $$ajournal
000270812 980__ $$aVDB
000270812 980__ $$aUNRESTRICTED
000270812 980__ $$aI:(DE-2719)5000005
000270812 980__ $$aI:(DE-2719)1210016
000270812 9801_ $$aFullTexts