Zeng Yi's group discovered the mechanism by which Zeb1 regulates vascular endothelial stem cell rest

On November 22, Cell Reports published online the latest research results of Zeng Yi Research Group of the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences, "Activation of Wnt/β-catenin signaling by Zeb1 in endothelial progenitors induces vascular quiescence" entry”
。 This study revealed the mechanism
by which Zeb1 regulates the resting state of vascular endothelial stem cells by regulating the Wnt/β-catenin signaling pathway.

The vascular circulatory system is essential
for the development and damage repair of various tissues and organs of the organism.
Through new generation, expansion and remodeling, blood vessels establish an effective supply network in various organs and maintain tissue homeostasis
.
When an adequate vascular network is formed, endothelial stem cells that dominate angiogenesis transition from an active proliferative state to a resting state, and imbalances in resting regulation can lead to excessive vascular growth and vascular disease
.
Accurate regulation of resting and activation of endothelial stem cells is key
to maintaining vascular homeostasis in tissues.
However, the mechanism that regulates endothelial stem cells into a resting state remains unclear
.

Previous research by Zeng Yi's team revealed the specific protein marker Procr for adult vascular endothelial stem cells (Cell Research 2016), and further discovered that Procr+ endothelial progenitor cells also exist in the early embryonic development stage (Development 2022).

In this study, Zeng Yi's research group discovered and resolved the molecular mechanism
of Zeb1 regulating the resting state of vascular endothelial stem cells.
During resting establishment, the expression level of Zeb1 was rapidly upregulated
with the downregulation of endothelial stem cell proliferative activity.
Moreover, specific Zeb1 knockout was found in mouse models to cause persistent proliferation of vascular endothelial cells, leading to vascular hyperplasia and vascular malformation
.
Through the binding analysis of RNA-seq and ATAC-seq, it was found that Zeb1 inhibited the proliferation of endothelial stem cells by directly inhibiting the expression of Wif1, thereby activating the Wnt/β-catenin signaling pathway.
Inhibition of Wif1 can save the continuous proliferation
of endothelial stem cells caused by Zeb1 deletion.
More importantly, activating the Wnt/β-catenin signaling pathway by local injection of NGS in vivo during the development stage of entering the resting state can effectively improve the angiodevelopmental defects
of Zeb1 mutants.
This work reveals that Zeb1, as an important checkpoint in the process of angiodevelopment, regulates the activity state of endothelial stem cells through the Zeb1-Wif1-Wnt/β-catenin signaling axis to ensure the establishment
of vascular homeostasis.
At the same time, pharmacological activation of a new Wnt/β-catenin signal is provided as a potential treatment for
angioproliferative diseases.

Yu Qing, associate researcher of the Center of Excellence for Molecular Cells, and Geng Ajun, a postdoctoral fellow at the Hangzhou Institute for Advanced Study of the National University of Science and Technology, are co-first authors
.
Researcher Zeng Yi, Associate Professor Yu Qing and Tom H.
Cheung of the Hong Kong University of Science and Technology are co-corresponding authors, and Professor Zeng Yi is also a part-time researcher
of the Hangzhou Institute for Advanced Study of the National University of Science and Technology.
This work was supported
by the team of researchers Bao Lan of the Center of Excellence for Molecular Cells, the team of Weijun Pan of the Shanghai Institute of Nutrition and Health, and Professor Yujie Chen of the quantitative biology quality control platform.
The achievement was supported by the Chinese Academy of Sciences, the National Natural Science Foundation of China and the Ministry of Science and Technology, as well as the Animal Platform, Cell Analysis Platform and Chemical Biology Platform of the Center of Excellence for Molecular Cells
.

Article link:

Zeb1 regulates resting endothelial stem cells via the Wif1-Wnt/β-Catenin signaling pathway