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

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http://hdl.handle.net/10138/251190

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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

Titel: Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation
Författare: Ihermann-Hella, Anneliis; Hirashima, Tsuyoshi; Kupari, Jussi; Kurtzeborn, Kristen; Li, Hao; Kwon, Hyuk Nam; Cebrian, Cristina; Soofi, Abdul; Dapkunas, Arvydas; Miinalainen, Ilkka; Dressler, Gregory R.; Matsuda, Michiyuki; Kuure, Satu
Upphovmannens organisation: Helsinki Institute of Life Science HiLIFE, Joint Activities
Kidney development
Medicum
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Helsinki Institute of Life Science HiLIFE, Infra
Datum: 2018-10-09
Språk: eng
Sidantal: 17
Tillhör serie: Stem cell reports
ISSN: 2213-6711
DOI: https://doi.org/10.1016/j.stemcr.2018.08.012
Permanenta länken (URI): http://hdl.handle.net/10138/251190
Abstrakt: 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.
Subject: KIDNEY DEVELOPMENT
METANEPHRIC MESENCHYME
SELF-RENEWAL
CELLS
SIX2
GENE
NEPHROGENESIS
ADHESION
KINASES
MORPHOGENESIS
3111 Biomedicine
Referentgranskad: Ja
Licens: cc_by_nc_nd
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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