LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells

María Ángeles Marqués-Torrejón, Charles A. C. Williams, Benjamin Southgate, Neza Alfazema, Melanie P. Clements, Claudia Garcia-Diaz, Carla Blin, Nerea Arranz-Emparan, Jane Fraser, Noor Gammoh, Simona Parrinello and Steven M. Pollard ()
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María Ángeles Marqués-Torrejón: University of Edinburgh
Charles A. C. Williams: University of Edinburgh
Benjamin Southgate: University of Edinburgh
Neza Alfazema: University of Edinburgh
Melanie P. Clements: University College London
Claudia Garcia-Diaz: University College London
Carla Blin: University of Edinburgh
Nerea Arranz-Emparan: University of Edinburgh
Jane Fraser: University of Edinburgh
Noor Gammoh: University of Edinburgh
Simona Parrinello: University College London
Steven M. Pollard: University of Edinburgh

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signaling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence.

Date: 2021
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DOI: 10.1038/s41467-021-22813-w

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