Vascular growth and remodeling are dependent on the generation of new endothelial cells from stem cells while vessel integrity and function are stabilized and maintained by embracing pericytes. Over the years, the cellular hierarchy and the identity of the stem cell in endothelium have remained unclear. Moreover, the dogma is that pericytes are “recruited” from mesenchymal progenitors and “adhered” to the outer of endothelium.
A research team led by Prof. ZENG Yi, at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences(CAS), established that Protein C receptor-expressing (Procr+) endothelial cells as VESCs in multiple tissues, including the mammary gland, skin and retina. This work was published in Cell Research.
Zeng’s group utilized a series of in vivo approaches, including lineage tracing using genetically modified mice, cell transplantation, developmental model system as well as hindlimb ischemia injury models to investigate and characterize Procr+ VESCs behavior inside the body system. The clonogenicity and endothelial properties of Procr+ VESCs were also assessed through in vitro assays.
Procr+ VESCs exhibit robust clonogenicity in culture, high vessel reconstitution efficiency in transplantation, long-term clonal expansion in lineage tracing, and Endothelial-to-Mesenchymal transition (EndMT) characteristics. Remarkably, Procr+ VESCs are bipotent, giving rise to de novo formation of endothelial cells and pericytes. This represents a novel origin of pericytes in adult angiogenesis, reshaping our understanding of blood vessel development and homeostatic process.
This work establishes that 1) Procr+ endothelial cells are stem cells in the vasculature of multiple organs, including the mammary gland, skin, retina and brain, and 2) Procr+ VESCs give rise to both endothelial cell and pericytes during development and homeostasis. Our work provides the first evidence for the de novo formation of pericytes from local endothelial stem cells. This finding challenges the current paradigm of a linear endothelial lineage, adding pericytes under the endothelial stem cells hierarchy.
This study may provide more precise therapeutic targets to inhibit pathological angiogenesis and tumor growth, providing new insight into the cellular contribution towards fibrotic disorders.
The study, entitled "Identification of Blood Vascular Endothelial Stem Cells by The Expression of Protein C Receptor" was published in the journal Cell Research on July 1st, 2016. Dr. YU Qing Cissy is the first author of the paper.
This work was supported by grants from the Ministry of Science and Technology of China and National Natural Science Foundation of China.
AUTHOR CONTACT:
Professor ZENG Yi Arial, Principal Investigator
State Key Laboratory of Cell Biology,
CAS Center for Excellence in Molecular Cell Science, SIBCB, Shanghai, China.
E-mail: yzeng@sibcb.ac.cn
Phone: +86-21-54921433
KEYWORDS: endothelial stem cell, pericytes, angiogenesis, vascular remodelling.
Legend: (Left) In the old model, the existence and cellular identity of vascular endothelial stem cells (VESCs) remain unclear. The perivascular pericytes in adult tissues are thought to arise from the recruitment and differentiation of mesenchymal progenitors during early development. (Right) The current study identifies Procr+ endothelial cells as bipotent VESCs that give rise to both endothelial cells and de novel formation of pericytes. (Image provided by Prof. ZENG Yi’s lab)
NEWS ABSTRACT:
This study identified vascular endothelial stem cells (VESCs) by the molecular marker of Procr. Though both in vitro and in vivo studies it has been revealed that Procr+ VESCs actively contributed to the angiogenesis of vasculature during development, as well as their bipotential in giving rise to pericytes during vessel formation in multiple organs. This work reshaped our current understanding on endothelial hierarchy and discovered a novel pericytes origin, which altogether might shield light on providing more precise therapeutic target in the treatment of pathological angiogenesis.
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