About this Biochemistry, Genetics and Molecular Biology article

Single-nucleus RNA-seq identifies divergent populations of FSHD2 myotube nuclei by Jiang, Shan; Williams, Katherine; Kong, Xiangduo; Zeng, Weihua; Nguyen, Nam Viet; Ma, Xinyi; Tawil, Rabi; Yokomori, Kyoko; Mortazavi, Ali; Scialdone, Antonio is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

FSHD is characterized by the misexpression of __DUX4__ in skeletal muscle. Although __DUX4__ upregulation is thought to be the pathogenic cause of FSHD, __DUX4__ is lowly expressed in patient samples, and analysis of the consequences of __DUX4__ expression has largely relied on artificial overexpression. To better understand the native expression profile of __DUX4__ and its targets, we performed bulk RNA-seq on a 6-day differentiation time-course in primary FSHD2 patient myoblasts. We identify a set of 54 genes upregulated in FSHD2 cells, termed FSHD-induced genes. Using single-cell and single-nucleus RNA-seq on myoblasts and differentiated myotubes, respectively, we captured, for the first time, __DUX4__ expressed at the single-nucleus level in a native state. We identified two populations of FSHD myotube nuclei based on low or high enrichment of __DUX4__ and FSHD-induced genes (“FSHD-Lo” and “FSHD Hi”, respectively). FSHD-Hi myotube nuclei coexpress multiple DUX4 target genes including __DUXA__, __LEUTX__ and __ZSCAN4__, and also upregulate cell cycle-related genes with significant enrichment of E2F target genes and p53 signaling activation. We found more FSHD-Hi nuclei than __DU

Author

Jiang, Shan; Williams, Katherine; Kong, Xiangduo; Zeng, Weihua; Nguyen, Nam Viet; Ma, Xinyi; Tawil, Rabi; Yokomori, Kyoko; Mortazavi, Ali; Scialdone, Antonio

Publisher

Public Library of Science; San Francisco CA: Public Library of Science, ©2005-; Public Library of Science (PLoS) (ISSN 1553-7390)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)