Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation

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dc.contributor.author Ihermann-Hella, Anneliis
dc.contributor.author Hirashima, Tsuyoshi
dc.contributor.author Kupari, Jussi
dc.contributor.author Kurtzeborn, Kristen
dc.contributor.author Li, Hao
dc.contributor.author Kwon, Hyuk Nam
dc.contributor.author Cebrian, Cristina
dc.contributor.author Soofi, Abdul
dc.contributor.author Dapkunas, Arvydas
dc.contributor.author Miinalainen, Ilkka
dc.contributor.author Dressler, Gregory R.
dc.contributor.author Matsuda, Michiyuki
dc.contributor.author Kuure, Satu
dc.date.accessioned 2018-10-18T05:17:02Z
dc.date.available 2018-10-18T05:17:02Z
dc.date.issued 2018-10-09
dc.identifier.citation Ihermann-Hella , A , Hirashima , T , Kupari , J , Kurtzeborn , K , Li , H , Kwon , H N , Cebrian , C , Soofi , A , Dapkunas , A , Miinalainen , I , Dressler , G R , Matsuda , M & Kuure , S 2018 , ' Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation ' , Stem cell reports , vol. 11 , no. 4 , pp. 912-928 . https://doi.org/10.1016/j.stemcr.2018.08.012
dc.identifier.other PURE: 117020602
dc.identifier.other PURE UUID: 7d8f0b51-0ded-48ce-a2a7-47c6c9a642cc
dc.identifier.other WOS: 000446691800008
dc.identifier.other ORCID: /0000-0002-9076-0622/work/49701730
dc.identifier.other Scopus: 85054712629
dc.identifier.other ORCID: /0000-0002-2254-1110/work/52866851
dc.identifier.uri http://hdl.handle.net/10138/251190
dc.description.abstract The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Forster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK activity regulates niche organization and communication with extracellular matrix through PAX2 and ITGA8, and is needed for CITED1 expression denoting undifferentiated status. MAPK/ERK activation in nephron precursors propels differentiation by priming cells for distal and proximal fates induced by the Wnt and Notch pathways. Thus, our results demonstrate a mechanism through which MAPK/ERK activity controls both progenitor maintenance and differentiation by regulating a distinct set of targets, which maintain the biomechanical milieu of tissue-residing progenitors and prime precursors for nephrogenesis. en
dc.format.extent 17
dc.language.iso eng
dc.relation.ispartof Stem cell reports
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject KIDNEY DEVELOPMENT
dc.subject METANEPHRIC MESENCHYME
dc.subject SELF-RENEWAL
dc.subject CELLS
dc.subject SIX2
dc.subject GENE
dc.subject NEPHROGENESIS
dc.subject ADHESION
dc.subject KINASES
dc.subject MORPHOGENESIS
dc.subject 3111 Biomedicine
dc.title Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation en
dc.type Article
dc.contributor.organization Helsinki Institute of Life Science HiLIFE, Joint Activities
dc.contributor.organization Kidney development
dc.contributor.organization Medicum
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization Helsinki Institute of Life Science HiLIFE, Infra
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.stemcr.2018.08.012
dc.relation.issn 2213-6711
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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