TY - JOUR
T1 - Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids
AU - Randriamanantsoa, S.
AU - Papargyriou, A.
AU - Maurer, H. C.
AU - Peschke, K.
AU - Schuster, M.
AU - Zecchin, G.
AU - Steiger, K.
AU - Öllinger, R.
AU - Saur, D.
AU - Scheel, C.
AU - Rad, R.
AU - Hannezo, E.
AU - Reichert, M.
AU - Bausch, A. R.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.
AB - The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85137221578&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-32806-y
DO - 10.1038/s41467-022-32806-y
M3 - Article
C2 - 36064947
AN - SCOPUS:85137221578
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5219
ER -