TY - JOUR
T1 - Beyond 2D
T2 - A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue
AU - Yamada, Hiroyuki
AU - Makino, Shin Ichi
AU - Okunaga, Issei
AU - Miyake, Takafumi
AU - Yamamoto-Nonaka, Kanae
AU - Trejo, Juan Alejandro Oliva
AU - Tominaga, Takahiro
AU - Empitu, Maulana A.
AU - Kadariswantiningsih, Ika N.
AU - Kerever, Aurelien
AU - Komiya, Akira
AU - Ichikawa, Tomohiko
AU - Arikawa-Hirasawa, Eri
AU - Yanagita, Motoko
AU - Asanuma, Katsuhiko
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-μm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.
AB - The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-μm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.
UR - http://www.scopus.com/inward/record.url?scp=85182375707&partnerID=8YFLogxK
U2 - 10.1093/pnasnexus/pgad433
DO - 10.1093/pnasnexus/pgad433
M3 - Article
AN - SCOPUS:85182375707
SN - 2752-6542
VL - 3
JO - PNAS Nexus
JF - PNAS Nexus
IS - 1
M1 - pgad433
ER -