Dataset Information

Identification of transcriptional drifts in endothelial cells associated with environmental changes

ABSTRACT: Environmental cues, such as shear stress and heterotypic cell interactions play a critical role in endothelial cell function, yet their unique contributions to the endothelial cell transcriptome remain unclear. Using cell preparations from human umbilical cords (ex vivo), we performed individual sample analysis to assess transcriptional drifts associated with environmental changes but independent of sex or background. Global gene expression profiling by RNA-seq, ATACseq, and MS/MS directed proteomics distinguished freshly isolated endothelial cells from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Amongst several signatures, we observed that TGF-beta and BMP target genes were reduced. In contrast, cytoskeleton-based processes and proliferation-related genes were increased. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes including targets of BMP and Notch signaling known to be sensitive to flow. In contrast, co-culture of endothelial cells with smooth muscle cells normalized networks related to cell growth and differentiation, clathrin-vesicle related genes, and recovered targets downstream TGF-beta, recovering approximately 9% of the original in vivo signature. Our findings highlight specific genes, pathways and functional features of endothelial cells that require contextual information and exposure to physical forces. This transcriptional modulation is important to consider in all paradigms that are focused on understanding the ability of endothelial cells to maintain homeostasis and respond to disease processes.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell

SUBMITTER: Yasi Jami

LAB HEAD: Luisa Iruela-Arispe

PROVIDER: PXD020958 | Pride | 2023-07-20

REPOSITORIES: Pride

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			Action	DRS
	2019-03-03-140min-200nl-yj-Yalda-Afshar-Luisa-Iruela-Arispe-TEST-P1-Ya113-A.mzML	Mzml
	2019-03-03-140min-200nl-yj-Yalda-Afshar-Luisa-Iruela-Arispe-TEST-P1-Ya113-A.mzXML	Mzxml
	2019-03-03-140min-200nl-yj-Yalda-Afshar-Luisa-Iruela-Arispe-TEST-P1-Ya113-A.raw	Raw
	2019-03-03-140min-200nl-yj-Yalda-Afshar-Luisa-Iruela-Arispe-TEST-P1-Ya115-A.mzML	Mzml
	2019-03-03-140min-200nl-yj-Yalda-Afshar-Luisa-Iruela-Arispe-TEST-P1-Ya115-A.mzXML	Mzxml

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Transcriptional drifts associated with environmental changes in endothelial cells.

Afshar Yalda Y Ma Feyiang F Quach Austin A Jeong Anhyo A Sunshine Hannah L HL Freitas Vanessa V Jami-Alahmadi Yasaman Y Helaers Raphael R Li Xinmin X Pellegrini Matteo M Wohlschlegel James A JA Romanoski Casey E CE Vikkula Miikka M Iruela-Arispe M Luisa ML

eLife 20230327

Environmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNA sequencing and protein expression by liquid chromatography-mass spe ...[more]

PMID: 36971339

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