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Effect of HES1 and HES4 on gene expression in A549 cells

ABSTRACT: Effect of HES1 and HES4 on gene expression in A549 cells

PROVIDER: PRJNA982839 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24900251_1.fastq.gz	Fastqsanger.gz
	SRR24900251_2.fastq.gz	Fastqsanger.gz
	SRR24900252_1.fastq.gz	Fastqsanger.gz
	SRR24900252_2.fastq.gz	Fastqsanger.gz
	SRR24900253_1.fastq.gz	Fastqsanger.gz

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HES1 and HES4 have both unique and overlapping roles as downstream mediators of Notch-dependent hematopoietic lineage decisions in human

Project description:In both mouse and human, Notch1 activation is the main initial driver to induce T-cell development in hematopoietic progenitor cells. The initiation of this developmental process coincides with Notch1-dependent repression of differentiation towards other hematopoietic lineages. Although well described in mice, the role of the individual Notch1 target genes during these hematopoietic developmental choices is still unclear in human. Here, we investigated the functional capacity of the Notch1 target genes HES1 and HES4 to modulate human Notch1-dependent hematopoietic lineage decisions. Using well-established in vitro cocultures and RNA sequencing, we show that HES1 acts as a repressor of differentiation by maintaining a quiescent stem cell signature in CD34+ hematopoietic progenitor cells. While HES4 can also inhibit NK and myeloid development like HES1, it acts differently on the T- versus B-cell lineage choice. Surprisingly, HES4 is not capable of repressing B-cell development, the most sensitive hematopoietic lineage with respect to Notch-mediated repression. In contrast to HES1, HES4 promotes initiation of early T-cell development. Overall, we show that the Notch1 target genes HES1 and HES4 display both unique and overlapping functions downstream of Notch during human hematopoietic lineage decisions.

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Project description:In the current investigation, an RNA-seq analysis was conducted to examine the differentially expressed genes in old ADSCs (O-ADSCs) following the overexpression of HES1. The findings indicated that 448 genes exhibited increased levels, while 865 genes showed decreased levels in the oe-HES1 O-ADSCs compared to the oe-NC O-ADSCs. The GO analysis revealed that these genes are primarily localized in the nucleus and cytoplasm, and are involved in activities such as protein binding and DNA binding. Furthermore, they are associated with processes related to cell adhesion and the regulation of transcription by RNA polymerase II. The KEGG analysis indicated enrichment in pathways such as the NOD-like receptor signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway.

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