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Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and Notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients

ABSTRACT: Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and Notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients

PROVIDER: PRJNA899793 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22244838_1.fastq.gz	Fastqsanger.gz
	SRR22244838_2.fastq.gz	Fastqsanger.gz
	SRR22244839_1.fastq.gz	Fastqsanger.gz
	SRR22244839_2.fastq.gz	Fastqsanger.gz

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Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and Notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients

Project description:Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with DNAH5 mutation. We found abnormal ciliary function and a decreased immune response caused by DNAH5 mutation through single-cell RNA sequencing (scRNA-seq).

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Multiomics analysis of a DNAH5-mutated PCD organoid model revealed the key role of the TGF-β/BMP and Notch pathways in epithelial differentiation and the immune response in DNAH5-mutated patients

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Project description:This SuperSeries is composed of the SubSeries listed below. 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.

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Project description: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.

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Extensive Crosstalk between BMP and Notch Signaling Pathways in Activated Adult Muscle Stem Cells [RNA-seq I]

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