Title:
Multicellular behavior and transcriptional network in angiogenic morphogenesis

 

Speaker:
Hiroki Kurihara, M.D., Ph.D.
Department of Physiological Chemistry and Metabolism,
The University of Tokyo Graduate School of Medicine
kuri-tky@umin.net

 

Abstract:
Angiogenesis is a morphogenetic process where new blood vessels are formed by sprouting and elongation of endothelial cells (ECs) from pre-existing vessels. This process is driven by complex EC movement characterized by positional mixing of cells moving toward different directions and mutual overtaking involving tip cells. The ability of ECs to build ordered branching structures through such a complex behavior is likely intrinsic. We recently identified a unique mode of coupled EC movements, which may serve as an elementary process in the directional migration of ECs during branch elongation. Cadherin-mediated cell contact is critical for this coordinated EC movements. Deterministic mathematical models based on these findings well simulate some aspects of angiogenesis. Further, single-cell transcriptome analysis revealed differential gene expression profiles in sprout formation, which include genes involved in the ‘tip cell’ phenotype and endothelial-mesenchymal transition. In the seminar, I will discuss what is ‘endothelialness’, how it is generated, and how it enables branching morphogenesis.

 

References:
Arima S, Nishiyama K, Ko T, Arima Y, Hakozaki Y, Sugihara K, Koseki H, Uchijima Y, Kurihara Y, Kurihara H. Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial cell movement. Development. 138(21): 4763-76, 2011.
Sugihara K, Nishiyama K, Fukuhara S, Uemura A, Arima S, Kobayashi R, Köhn-Luque A, Mochizuki N, Suda T, Ogawa H, Kurihara H. Autonomy and non-autonomy of angiogenic cell movements revealed by experiment-driven mathematical modeling. Cell Rep. 13(9): 1814-1827, 2015.
Matsuya K, Yura F, Mada J, Kurihara H, Tokihiro T. A discrete mathematical model for angiogenesis. SIAM J. Appl. Math. 76(6):2243–2259, 2016.