백지응 (University of California, Berkeley, 이화여자대학교)

한빛사논문

조회244

University of California, Berkeley, 이화여자대학교

CV File 351 kb

Sci. Adv., Aug 02 2024, 10 (31) | https://doi.org/10.1126/sciadv.adk8232 Spectrin mediates 3D-specific matrix stress-relaxation response in neural stem cell lineage commitment

Eric Qiao ^1†, Jieung Baek ^2,3†, Camille Fulmore ⁴, Myoung Song ⁵, Taek-Soo Kim⁵, Sanjay Kumar ^1,2,6*, David V Schaffer ^1,2,7*

¹Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA.

²Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.

³Department of Mechanical and Biomedical Engineering, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul 03760, Republic of Korea.

⁴Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

⁵Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

⁶Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.

⁷Helen Wills Neuroscience Institute, Berkeley, CA 94720, USA.

^*Corresponding authors: S.K.; D.V.S.

^†These authors contributed equally to this work.

Abstract

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.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-05)
연구진국내+국외 연구진
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