Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion

Author(s):Show less -

Alves, Chrystian Junqueira ^[1] ; Dariolli, Rafael ^[2] ; Haydak, Jonathan ^[3] ; Kang, Sangjo ^[1] ; Hannah, Theodore ^[1] ; Wiener, Robert J. ^[4] ; DeFronzo, Stefanie ^[3] ; Tejero, Rut ^[1] ; Gusella, Gabriele L. ^[3] ; Ramakrishnan, Aarthi ^[1] ; Dias, Rodrigo Alves ^[5] ; Wojcinski, Alexandre ^{[6, 7]} ; Kesari, Santosh ^{[6, 7]} ; Shen, Li ^[1] ; Sobie, Eric A. ^[2] ; Furtado de Mendonca, Jose Paulo Rodrigues ^[5] ; Azeloglu, Evren U. ^{[2, 3]} ; Zou, Hongyan ^{[1, 8]} ; Friedel, Roland H. ^{[1, 8]}

Affiliation

^[1] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Nash Family Dept Neurosci, New York, NY 10029 - USA

^[2] Icahn Sch Med Mt Sinai, Dept Pharmacol Sci, New York, NY 10029 - USA

^[3] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 - USA

^[4] Icahn Sch Med Mt Sinai, Dept Med, Div Cardiol, New York, NY 10029 - USA

^[5] Univ Fed Juiz de Fora, Dept Phys, Juiz De Fora - Brazil

^[6] Pacific Neurosci Inst, Santa Monica, CA - USA

^[7] Providence St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA - USA

^[8] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 - USA

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 12, n. 1 OCT 14 2021.
• Web of Science Citations: 0

Abstract

Biomechanical mechanisms orchestrating stem cell dynamics in development remain unclear. Here the authors show that guidance receptor Plexin-B2 organizes actomyosin contractility, cytoskeletal tension and adhesion during multicellular development of human embryonic stem cells and neuroprogenitor cells. During morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosin contractility, leading to changes in cell stiffness and cytoskeletal tension, as well as cell-cell and cell-matrix adhesion. We have delineated the functional domains of Plexin-B2, RAP1/2 effectors, and the signaling association with ERK1/2, calcium activation, and YAP mechanosensor, thus providing a mechanistic link between Plexin-B2-mediated cytoskeletal tension and stem cell physiology. Plexin-B2-deficient stem cells exhibit premature lineage commitment, and a balanced level of Plexin-B2 activity is critical for maintaining cytoarchitectural integrity of the developing neuroepithelium, as modeled in cerebral organoids. Our studies thus establish a significant function of Plexin-B2 in orchestrating cytoskeletal tension and cell-cell/cell-matrix adhesion, therefore solidifying the importance of collective cell mechanics in governing stem cell physiology and tissue morphogenesis. (AU)

• FAPESP's process: 16/07541-5 - Action potential and Calcium transient phenotyping of cardiomyocytes derived from pluripotent stem cells: development of an electrophysiological platform CM-PSCs compatible to study disease and drug modeling and cardiac regeneration approaches
• Grantee: Rafael Dariolli
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor