Spatiotemporal heterogeneity and patterning of developing renal blood vessels

Abstract

The kidney vasculature facilitates the excretion of wastes, the dissemination of hormones, and the regulation of blood chemistry. To carry out these diverse functions, the vasculature is regionalized within the kidney and along the nephron. However, when and how endothelial regionalization occurs remains unknown. Here, we examine the developing kidney vasculature to assess its 3-dimensional structure and transcriptional heterogeneity. First, we observe that endothelial cells (ECs) grow coordinately with the kidney bud as early as E10.5, and begin to show signs of specification by E13.5 when the first arteries can be identified. We then focus on how ECs pattern and remodel with respect to the developing nephron and collecting duct epithelia. ECs circumscribe nephron progenitor populations at the distal tips of the ureteric bud (UB) tree and form stereotyped cruciform structures around each tip. Beginning at the renal vesicle (RV) stage, ECs form a continuous plexus around developing nephrons. The endothelial plexus envelops and elaborates with the maturing nephron, becoming preferentially enriched along the early distal tubule. Lastly, we perform transcriptional and immunofluorescent screens to characterize spatiotemporal heterogeneity in the kidney vasculature and identify novel regionally enriched genes. A better understanding of development of the kidney vasculature will help instruct engineering of properly vascularized ex vivo kidneys and evaluate diseased kidneys.

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

“…These are mitochondrial apoptosis, endoplasmic reticulum‐related apoptosis and Fas‐mediated death . Notably, brain tissues contain abundant mitochondria which consistently supply energy to sustain brain function such as neurotransmitters release and neuronal survival . Mitochondrial apoptosis has been reported in the progression of cerebral IRI through a poorly understood mechanism .…”

“…9,10 Notably, brain tissues contain abundant mitochondria which consistently supply energy to sustain brain function such as neurotransmitters release and neuronal survival. 11,12 Mitochondrial apoptosis has been reported in the progression of cerebral IRI through a poorly understood mechanism. 13,14 At reperfusion stage, mitochondria produce the majority of ROS that are generated, and the latter alters the mitochondrial membrane potential.…”

Cyp26b1 is required for proper airway epithelial differentiation during lung development

“…For immunofluorescent stains, slides were baked at 60˚C for 10 min and allowed to cool down to room temperature before deparaffinizing in xylene 2 times for 5 min each and rehydrating through an ethanol series ending on brief wash in water. Once in aqueous solution, the stain was performed as described previously (Daniel et al, 2018). Briefly, slides were washed in PBS + 0.1% Triton-X 100 (Fisher Scientific, BP151-100) for 3 5min washes.…”

“…Cyp26b1 full coding sequence clone was acquired from Dharmacon (BC059246) and linearized using EcoRI. Probe synthesis was performed as described previously (Daniel et al, 2018). Briefly, probes were synthesized at 37˚C for 2-4 hrs in digoxigeninsynthesis reaction mixture with T3 RNA polymerase (Roche).…”

“…In situ hybridizations were performed as described previously (Daniel et al, 2018). Briefly, E12.5 -E18.5 embryos, lungs and kidneys were fixed and embedded in paraffin as described above.…”