Spectrin mediates 3D-specific matrix stress-relaxation response in neural stem cell lineage commitment.

Autor:	Qiao E; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA., Baek J; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.; Department of Mechanical and Biomedical Engineering, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul 03760, Republic of Korea., Fulmore C; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Song M; Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea., Kim TS; Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea., Kumar S; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA., Schaffer DV; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.; Helen Wills Neuroscience Institute, Berkeley, CA 94720, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Aug 02; Vol. 10 (31), pp. eadk8232. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1126/sciadv.adk8232
Abstrakt:	While extracellular matrix (ECM) stress relaxation is increasingly appreciated to regulate stem cell fate commitment and other behaviors, much remains unknown about how cells process stress-relaxation cues in tissue-like three-dimensional (3D) geometries versus traditional 2D cell culture. Here, we develop an oligonucleotide-crosslinked hyaluronic acid-based ECM platform with tunable stress relaxation properties capable of use in either 2D or 3D. Strikingly, stress relaxation favors neural stem cell (NSC) neurogenesis in 3D but suppresses it in 2D. RNA sequencing and functional studies implicate the membrane-associated protein spectrin as a key 3D-specific transducer of stress-relaxation cues. Confining stress drives spectrin's recruitment to the F-actin cytoskeleton, where it mechanically reinforces the cortex and potentiates mechanotransductive signaling. Increased spectrin expression is also accompanied by increased expression of the transcription factor EGR1, which we previously showed mediates NSC stiffness-dependent lineage commitment in 3D. Our work highlights spectrin as an important molecular sensor and transducer of 3D stress-relaxation cues.
Databáze:	MEDLINE
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