{"id":882,"date":"2018-08-14T18:36:52","date_gmt":"2018-08-14T18:36:52","guid":{"rendered":"https:\/\/research.med.virginia.edu\/pcen\/?page_id=882"},"modified":"2018-08-14T18:36:52","modified_gmt":"2018-08-14T18:36:52","slug":"the-fate-and-function-in-capillary-development-of-the-peri-ureteric-bud-pericytes-in-the-developing-mouse-renal-medulla","status":"publish","type":"page","link":"https:\/\/med.virginia.edu\/pcen\/main-projects\/the-fate-and-function-in-capillary-development-of-the-peri-ureteric-bud-pericytes-in-the-developing-mouse-renal-medulla\/","title":{"rendered":"Past Pilot Programs"},"content":{"rendered":"

Pilot Project 1: The fate and function in capillary development of the peri-ureteric bud pericytes in the developing mouse renal medulla<\/strong><\/p>\n

Principal Investigator: <\/strong>Jing Yu, Ph.D.<\/p>\n

Mentor: <\/strong>Ariel R. Gomez, M.D.<\/p>\n

The capillary network of the mammalian renal medulla plays a key role in the regulation of body water and electrolyte homeostasis which is critical for extrarenal wellness such as cardiovascular health and normal brain function. Despite its physiological importance, our knowledge on where this capillary network arises from and how they form is largely unexplored. Understanding the origin and the mechanisms underlying the formation of this vasculature network is not only important for the establishment of a functional kidney at the beginning of postnatal life, but will also facilitate efforts in repair and rebuilding of a renal medulla following damage and disease both in vivo<\/em> and in vitro<\/em>. Our previous work revealed that Wnt7b<\/em> signaling from the ureteric bud (UB) epithelium regulates lumen formation of the peri-UB capillaries in the nascent renal medulla of the developing mouse kidney. Wnt7b signals to the pericytes associated with this population of the capillaries, suggesting that these pericytes play a role in lumen formation of the capillaries that they are associated with. Our long term objective is to understand the fate of this population of pericytes in the adult stage in normal and abnormal conditions and the role they play in regulating capillary lumen formation<\/strong>. In this application, we propose to test the<\/strong> hypothesis that the pericytes of peri-UB capillaries in the developing renal medulla contributes to pericytes associated with the vasa recta in the adult stage and they act on endothelial cells to regulate the lumen formation of the medullary peri-UB capillaries (Figure 1).<\/strong> We will test this hypothesis in the following two specific aims,<\/p>\n

SA1. Determine the fate of the medullary peri-UB capillary pericytes at the adult stage <\/u><\/p>\n

\"\"\"\"<\/p>\n

In the developing mouse kidney, Neurotensin<\/em> (Nts<\/em>) is expressed in the renal medullary interstitium surrounding the ureteric bud epithelium, the pericytes of medullary peri-UB capillaries. A Nts-Cre<\/em> mouse strain where the Cre recombinase is expressed from the endogenous Nts<\/em> locus is available for us. We will employ Nts-Cre; mT\/mG<\/em> mice in which the Cre expressing cells and their progeny express GFP at the cell membrane. We will determine whether the GFP-expressing cells in the kidney at the adult stage are pericytes associated with vasa recta with co-immunostaining for GFP and vasculature markers such as Pdgfrb and Desmin (pericyte) and UT-B (descending vasa recta).<\/p>\n

SA2. Identify\u00a0signals from the pericytes to endothelial cells that promotes capillary lumen formation. <\/u><\/p>\n

We will sort out GFP+ cells from E15.5 Nts-Cre; mT\/mG<\/em> kidneys with Fluorescence-activated cell sorting (FACS), and perform single cell RNA-seq to identify, bioinformatically, genes encoding secreted proteins in these cells, especially in those cells that express Nts<\/em> and p57Kip2<\/em> (pericytes of medullary peri-UB capillaries). We will then perform in situ<\/em> hybridization or immunofluorescence staining to validate the expression in the pericytes of medullary peri-UB capillaries of these genes, with the top priority for genes implicated in vascular development in the literature.<\/p>\n

We will also develop a 3-D endothelial cell-pericyte co-culture system with HUVEC or endothelial colony forming cells (ECFC)-derived endothelial cells and the GFP+ cells sorted from E15.5 Nts-Cre; mT\/mG<\/em> kidneys.<\/p>\n

Lastly, we will screen the secreted factors, in particular genes implicated in vascular development in the literature, identified with RNA-seq and validated experimentally\u00a0for pericytes derived signals that promote endothelial lumen formation, using the 3-D co-culture system. We will\u00a0determine if endothelial tube lumen formation is\u00a0disrupted with blocking antibodies or small molecule inhibitors for these gene products, where available. Alternatively, if the secreted proteins are<\/p>\n

available, we\u00a0will\u00a0apply the proteins to the 3-D HUVEC or ECFC-derived endothelial cell culture to see if they promote endothelial tube lumen formation.<\/p>\n

The proposed work will serve as the basis for determining the fate of these pericytes and their progenies in renal diseases (acute and chronic kidney injuries) and repair, genetic analysis to determine the role of pericytes in medullary peri-UB capillary lumen formation in vivo<\/em>, and for engineering renal medullary capillaries in vitro<\/em>.<\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Pilot Project 1: The fate and function in capillary development of the peri-ureteric bud pericytes in the developing mouse renal medulla Principal Investigator: Jing Yu, Ph.D. Mentor: Ariel R. Gomez, M.D. The capillary network of the mammalian renal medulla plays a key role in the regulation of body water and electrolyte homeostasis which is critical […]<\/p>\n","protected":false},"author":1777,"featured_media":0,"parent":33,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"tags":[],"class_list":["post-882","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\nPast Pilot Programs - Pediatric Center of Excellence<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/pcen\/main-projects\/the-fate-and-function-in-capillary-development-of-the-peri-ureteric-bud-pericytes-in-the-developing-mouse-renal-medulla\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Past Pilot Programs - Pediatric Center of Excellence\" \/>\n<meta property=\"og:description\" content=\"Pilot Project 1: The fate and function in capillary development of the peri-ureteric bud pericytes in the developing mouse renal medulla Principal Investigator: Jing Yu, Ph.D. Mentor: Ariel R. 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