Mouse models are a tool for studying the mechanisms underlying complex diseases; however, differences between species pose a significant challenge for translating findings to patients. Here, we used single-cell transcriptomics and orthogonal validation approaches to provide cross-species taxonomies, identifying shared broad cell classes and unique granular cellular states, between mouse and human kidney. We generated cell atlases of the diabetic and obese kidney using two different mouse models, a high-fat diet (HFD) model and a genetic model (BTBR ob/ob), at multiple time points along disease progression. Importantly, we identified a previously unrecognized, expanding Trem2high macrophage population in kidneys of HFD mice that matched human TREM2high macrophages in obese patients. Taken together, our cross-species comparison highlights shared immune and metabolic cell-state changes.

To assess normal organization of frontostriatal brain wiring, we analyzed diffusion magnetic resonance imaging (dMRI) scans in 100 young adult healthy subjects (HSs). We identified fiber clusters intersecting the frontal cortex and caudate, a core component of associative striatum, and quantified their degree of deviation from a strictly topographic pattern. Using whole brain dMRI tractography and an automated tract parcellation clustering method, we extracted 17 white matter fiber clusters per hemisphere connecting the frontal cortex and caudate. In a novel approach to quantify the geometric relationship among clusters, we measured intercluster endpoint distances between corresponding cluster pairs in the frontal cortex and caudate. We show first, the overall frontal cortex wiring pattern of the caudate deviates from a strictly topographic organization due to significantly greater convergence in regionally specific clusters; second, these significantly convergent clusters originate in subregions of ventrolateral, dorsolateral, and orbitofrontal prefrontal cortex (PFC); and, third, a similar organization in both hemispheres. Using a novel tractography method, we find PFC-caudate brain wiring in HSs deviates from a strictly topographic organization due to a regionally specific pattern of cluster convergence. We conjecture cortical subregions projecting to the caudate with greater convergence subserve functions that benefit from greater circuit integration.

In this paper, we present a deep learning method, DDMReg, for fast and accurate registration between diffusion MRI (dMRI) datasets. In dMRI registration, the goal is to spatially align brain anatomical structures while ensuring that local fiber orientations remain consistent with the underlying white matter fiber tract anatomy. To the best of our knowledge, DDMReg is the first deep-learning-based dMRI registration method. DDMReg is a fully unsupervised method for deformable registration between pairs of dMRI datasets. We propose a novel registration architecture that leverages not only whole brain information but also tract-specific fiber orientation information. We perform comparisons with four state-of-the-art registration methods. We evaluate the registration performance by assessing the ability to align anatomically corresponding brain structures and ensure fiber spatial agreement between different subjects after registration. Experimental results show that DDMReg obtains significantly improved registration performance. In addition, DDMReg leverages deep learning techniques and provides a fast and efficient tool for dMRI registration.