RHO Proteins in RAS Signaling and Transformation

Karnoub, Antoine E.; Chenette, Emily J.; Der, Channing J.

doi:10.1007/1-4020-4708-8_7

Cited by 2 publications

(2 citation statements)

References 171 publications

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“…Shortened filopodia are consistent with early reports that showed rounding 3 overexpression promoted substantial filopodial extensions. 101 A connection between filopodia, which are prominently displayed on tip cells, and cell migration has been established. The absence of filopodia slowed tip cell migration during retinal angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3

Abbey,

Duran,

Chen

et al. 2024

ATVB

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BACKGROUND: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. METHODS: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from noninvading cells. We used this model to perform multiple transcriptomics analyses from independent donors to monitor endothelial gene expression changes. RESULTS: Single-cell population analyses, single-cell cluster analyses, and bulk RNA sequencing revealed common transcriptomic changes associated with invading cells. We also found that collagenase digestion used to isolate single cells upregulated the Fos proto-oncogene transcription factor. Exclusion of Fos proto-oncogene expressing cells revealed a gene signature consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis and included multiple tip cell markers. Upregulation of SNAI1 (snail family transcriptional repressor 1), PTGS2 (prostaglandin synthase 2), and JUNB (JunB proto-oncogene) protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated rounding 3, also known as RhoE, which has not yet been implicated in angiogenesis. Silencing rounding 3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for rounding 3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared with wild-type littermates. CONCLUSIONS: Validation of multiple genes, including rounding 3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.

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Section: Discussionmentioning

confidence: 99%

Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3

Abbey,

Duran,

Chen

et al. 2024

ATVB

View full text Add to dashboard Cite

show abstract

“…Shortened filopodia are consistent with early reports that indicate RND3 overexpression promoted substantial filopodial extensions. 69 A connection between filopodia, which are prominently displayed on tip cells and cell migration has been established. The absence of filopodia slowed tip cell migration during retinal angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of new markers of angiogenic sprouting using transcriptomics: New role for RND3

Abbey,

Duran,

Chen

et al. 2023

Preprint

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Background: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. Approach and Results: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from non-invading cells. We used this model to perform multiple transcriptomics analyses from multiple donors to monitor endothelial gene expression changes. Single-cell Population Analyses, single-cell Cluster Analyses, and bulk RNA sequencing were used to delineate transcriptomic changes in invading cells. The results revealed a 39 gene signature that was consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis, and include multiple tip cell markers. Upregulation of SNAI1, PTGS2, and JUNB protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated Rounding 3 (RND3), also known as RhoE, which has not yet been implicated in angiogenesis. Silencing RND3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for RND3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared to wild type littermates. Conclusion: Validation of multiple genes, including RND3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes that are associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.

show abstract

RHO Proteins in RAS Signaling and Transformation

Cited by 2 publications

References 171 publications

Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3

Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3

Identification of new markers of angiogenic sprouting using transcriptomics: New role for RND3

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