Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses.

Autor: Prahl LS; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA, USA., Liu J; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Viola JM; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Huang AZ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Chan TJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Hayward-Lara G; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Porter CM; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA., Shi C; Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA., Zhang J; Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA., Hughes AJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Center for Soft and Living Matter, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Bioengineering Graduate Group, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Center for Precision Engineering for Health (CPE4H), University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Materials Research Science and Engineering Center (MRSEC), University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA. ajhughes@seas.upenn.edu.
Jazyk: angličtina
Zdroj: Nature materials [Nat Mater] 2024 Nov; Vol. 23 (11), pp. 1582-1591. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1038/s41563-024-02019-3
Abstrakt: Urinary collecting tubules form during kidney embryogenesis through the branching of the ureteric bud epithelium. A travelling mesenchyme niche of nephron progenitor cells caps each branching ureteric bud tip. These 'tip domain' niches pack more closely over developmental time and their number relates to nephron endowment at birth. Yet, how the crowded tissue environment impacts niche number and cell decision-making remains unclear. Here, through experiments and mathematical modelling, we show that niche packing conforms to physical limitations imposed by kidney curvature. We relate packing geometries to rigidity theory to predict a stiffening transition starting at embryonic day 15 in the mouse, validated by micromechanical analysis. Using a method to estimate tip domain 'ages' relative to their most recent branch events, we find that new niches overcome mechanical resistance as they branch and displace neighbours. This creates rhythmic mechanical stress in the niche. These findings expand our understanding of kidney development and inform engineering strategies for synthetic regenerative tissues.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE