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Anneliis Ihermann-Hella, Tsuyoshi Hirashima, Jussi Kupari, Kristen Kurtzeborn, Hao Li, Hyuk Nam Kwon, Cristina Cebrian, Abdul Soofi, Arvydas Dapkunas, Ilkka Miinalainen, Gregory R. Dressler, Michiyuki Matsuda, Satu Kuure, Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation, Stem Cell Reports, Volume 11, Issue 4, 2018, Pages 912-928, ISSN 2213-6711, https://doi.org/10.1016/j.stemcr.2018.08.012.

Dynamic MAPK/ERK activity sustains nephron progenitors through niche regulation and primes precursors for differentiation

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Author: Ihermann-Hella, Anneliis1; Hirashima, Tsuyoshi2; Kupari, Jussi1,3;
Organizations: 1HiLIFE and Medicum, University of Helsinki
2Department of Pathology and Biology of Diseases, Graduate School of Medicine & Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University
3Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet
4Developmental Biology Division, Cincinnati Children’s Hospital
5Department of Pathology, University of Michigan
6Medicum and Meilahti Clinical Proteomics Core Facility/HiLIFE, University of Helsinki
7Department of Pathology (Biocenter Oulu), University of Oulu
8GM-Unit, LAC/ HiLIFE, and Medicum, University of Helsinki
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 10.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2018111948469
Language: English
Published: Elsevier, 2018
Publish Date: 2018-11-19
Description:

Summary

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 Förster 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.

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Series: Stem cell reports
ISSN: 2213-6711
ISSN-E: 2213-6711
ISSN-L: 2213-6711
Volume: 11
Issue: 4
Pages: 912 - 928
DOI: 10.1016/j.stemcr.2018.08.012
OADOI: https://oadoi.org/10.1016/j.stemcr.2018.08.012
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
MAPK/ERK activity
differentiation
intracellular signaling
kidney development
nephrogenesis
nephron progenitor
progenitor cells
self-renewal
signaling strength
stem cell niche
Article
Funding: This work was supported by grants to S.K. from the Academy of Finland (grants 294243 and 309997), Jane and Aatos Erkko, Sigrid Juselius, and Maud Kuistila Foundations, and A.I.-H. by a Doctoral program in Biomedicine, University of Helsinki.
Academy of Finland Grant Number: 294243
309997
Detailed Information: 294243 (Academy of Finland Funding decision)
309997 (Academy of Finland Funding decision)
Dataset Reference: Supplemental experimental procedures:
  https://ars.els-cdn.com/content/image/1-s2.0-S2213671118303564-mmc1.pdf
Copyright information: © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  https://creativecommons.org/licenses/by-nc-nd/4.0/