McLaughlin Liam, Zhang Bo, Sharma Siddharth, Knoten Amanda L, Kaushal Madhurima, Purkerson Jeffrey M, Huyck Heidie L, Pryhuber Gloria S, Gaut Joseph P, Jain Sanjay
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
Nat Commun. 2025 Jun 3;16(1):5161. doi: 10.1038/s41467-025-60435-8.
The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through "mother glomeruli" that serve as control centers, creating a repeating pattern throughout the cortex. This sophisticated neural organization, which is underdeveloped in newborn kidneys and disrupted in conditions like diabetes and hydronephrosis, appears to facilitate synchronized responses to maintain fluid balance. The findings provide insights into how the kidney's structural architecture enables coordinated function across its numerous nephrons.
人类肾脏通过由多达一百万个肾单位组成的复杂网络维持体内平衡，肾单位是其基本组织单位。利用创新的组织处理和光片荧光显微镜技术，我们绘制了肾单位的三维神经血管连接图，以了解其结构组织如何实现诸如过滤、吸收和血压调节等协调功能。我们的分析揭示了从出生到衰老过程中肾小球方向、密度、体积和神经支配的发育变化。我们发现了一个广泛的神经网络，它连接不同的肾单位节段，并将肾小球组织成不同的群落。这些群落通过作为控制中心的“母肾小球”相连，在整个皮质中形成重复模式。这种复杂的神经组织在新生肾脏中发育不全，在糖尿病和肾积水等情况下会受到破坏，似乎有助于维持液体平衡的同步反应。这些发现为肾脏的结构架构如何实现其众多肾单位的协调功能提供了见解。
