Heterogeneity of Satellite Cells Implicates DELTA1/NOTCH2 Signaling in Self-Renewal.

Valeria Yartseva, Leonard D Goldstein, Julia Rodman, Lance Kates, Mark Z Chen, Ying-Jiun J Chen, Oded Foreman, Christian W Siebel, Zora Modrusan, Andrew S Peterson, Ana Jovičić

Cell reports 2020 Feb 04

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How satellite cells and their progenitors balance differentiation and self-renewal to achieve sustainable tissue regeneration is not well understood. A major roadblock to understanding satellite cell fate decisions has been the difficulty of studying this process in vivo. By visualizing expression dynamics of myogenic transcription factors during early regeneration in vivo, we identify the time point at which cells undergo decisions to differentiate or self-renew. Single-cell RNA sequencing reveals heterogeneity of satellite cells, including a subpopulation enriched in Notch2 receptor expression, during both muscle homeostasis and regeneration. Furthermore, we reveal that differentiating cells express the Dll1 ligand. Using antagonistic antibodies, we demonstrate that the DLL1 and NOTCH2 signaling pair is required for satellite cell self-renewal. Thus, differentiating cells provide the self-renewing signal during regeneration, enabling proportional regeneration in response to injury while maintaining the satellite cell pool. These findings have implications for therapeutic control of muscle regeneration. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Valeria Yartseva, Leonard D Goldstein, Julia Rodman, Lance Kates, Mark Z Chen, Ying-Jiun J Chen, Oded Foreman, Christian W Siebel, Zora Modrusan, Andrew S Peterson, Ana Jovičić. Heterogeneity of Satellite Cells Implicates DELTA1/NOTCH2 Signaling in Self-Renewal. Cell reports. 2020 Feb 04;30(5):1491-1503.e6