Extensive crosstalk between BMP and notch signaling pathways in activated adult muscle stem cells

Lange, Birthe Katrin Alexandra; Polydorou, Ioanna; Huryn, Viktoriia; Morales-Gonzalez, Susanne; Brandt, Bettina; Birchmeier, Carmen; Amthor, Helge; Schuelke, Markus

Extensive crosstalk between BMP and notch signaling pathways in activated adult muscle stem cells

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Item Type:	Preprint
Title:	Extensive crosstalk between BMP and notch signaling pathways in activated adult muscle stem cells
Creators Name:	Lange, Birthe Katrin Alexandra, Polydorou, Ioanna, Huryn, Viktoriia, Morales-Gonzalez, Susanne, Brandt, Bettina, Birchmeier, Carmen, Amthor, Helge and Schuelke, Markus
Abstract:	Muscle stem cells (MuSC) are the cellular source for generation and regeneration of skeletal muscle. To ensure correct muscle growth, MuSC self-renewal and differentiation need to be tightly regulated. Several signaling systems have been implicated in the control of MuSCs, among them Bone Morphogenetic Proteins (BMPs) and Notch, both of which promote MuSC proliferation and suppress differentiation. To better understand the mechanisms of function and the target genes regulated by BMP signaling in myogenesis, we investigated the transcriptional responses of adult mouse MuSCs to BMP6/4 using RNA-sequencing. BMP6/4-stimulation of freshly isolated MuSCs for one hour rapidly increased the expression of classical BMP target genes like Id1 and strongly induced expression of genes of the Notch pathway (Hes1, Hey1, Lfng, Snai1). In parallel, using Cleavage Under Targets and Tagmentation (CUT&Tag), we generated whole-genome binding profiles for the BMP pathway effectors pSMAD1/5/9 and SMAD4 and detected binding in promoters and potential regulatory elements of BMP targets and Notch pathway genes (Hes1, Hey1, Lfng, Snai1) indicating that BMP signaling directly influences Notch and that crosstalk between the two pathways regulates myogenesis.
Keywords:	Bone Morphogenetic Protein, Notch Pathway, Adult Muscle Stem Cell, Mouse, RNA-Sequencing, Transcription Factor Binding Site, pSMAD1/5/9, SMAD4, CUT&Tag, Animals, Mice
Source:	Preprints.org
Publisher:	MDPI
Article Number:	202603.1228
Date:	16 March 2026
Official Publication:	https://doi.org/10.20944/preprints202603.1228.v1
Related to:	URL URL Type https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306430 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159594 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127798 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305746 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305745 External Dataset

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