Author:
Martínez-Torres Dilan,Maldonado Valentina,Pérez-Gallardo Cristian,Yañez Rodrigo,Candia Valeria,Kalaidzidis Yannis,Zerial Marino,Morales-Navarrete Hernán,Segovia-Miranda Fabián
Abstract
AbstractThree-dimensional (3D) geometrical models are potent tools for quantifying complex tissue features and exploring structure–function relationships. However, these models are generally incomplete due to experimental limitations in acquiring multiple (> 4) fluorescent channels in thick tissue sections simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we combined deep-tissue immunostaining, multiphoton microscopy, deep-learning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatial single-cell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the effect on the liver's overall structure when changing the hepatic environment after removing KCs. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs results in morphological changes in hepatocytes and HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, opening up avenues for in-depth investigations into tissue structure across both normal and pathological conditions.
Funder
Fondo Nacional de Desarrollo Científico y Tecnológico
Publisher
Springer Science and Business Media LLC
Reference70 articles.
1. Treyer, A. & Müsch, A. Hepatocyte polarity. Compr. Physiol. 3, 243–287 (2013).
2. Bogdanos, D. P., Gao, B. & Gershwin, M. E. Liver immunology. Compr. Physiol. 3, 567–598 (2013).
3. Tsuchida, T. & Friedman, S. L. Mechanisms of hepatic stellate cell activation. Nat. Rev. Gastroenterol. 14, 397–411 (2017).
4. Dixon, L. J., Barnes, M., Tang, H., Pritchard, M. T. & Nagy, L. E. Comprehensive Physiology Vol. 3 (Wiley, 2013).
5. Li, N. & Hua, J. Immune cells in liver regeneration. Oncotarget 8, 3628 (2015).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献