Innovative Technology Enhances Cellular and Molecular Insights into Kidney Lesions

Researchers have demonstrated the feasibility of a morphological-based approach to interpreting spatial transcriptomic (ST) data, helping to improve understanding of the lesions that occur in chronic kidney disease (CKD), at both the cellular and molecular levels. A recent studyopens in new tab/window in The American Journal of Pathologyopens in new tab/window, published by Elsevier, details how this new method could lead to the identification of new biomarkers and therapeutic strategies for patients.

ST technologies are a rapidly developing new tool for measuring RNA in their original spatial context, giving a molecular mechanistic dimension to tissue morphology. The application of ST technologies has already yielded important insights across many different tissues and disease models. By combining profiling of gene expression patterns with the spatial information of cells in tissues, ST provides a more complete understanding of the molecular and cellular organization of tissues and lesions.

Lead investigator Benjamin D. Humphreys, MD, PhD, Division of Nephrology, Department of Medicine, and the Department of Developmental Biology, Washington University in St. Louis, explains, "During ST data analysis, computationally-annotated clusters are often superimposed on a histological image. However, tissue morphology by standard light microscopic pathologic evaluation is not considered. This may preclude assimilation of important information that can help interpret the ST data. The kidney is a particularly heterogeneous organ in morphologic terms, with a high degree of spatial and temporal lesion variability often present in pathologic situations. We conducted a histopathological-based analysis of spatial transcriptomics on four human kidney samples with CKD, corresponding as closely as possible to how a kidney biopsy is interpreted in clinical practice."

The study demonstrates how:

• Morphological and ST cross-analysis can help identify lesions within tissues such as tertiary lymphoid organs in the kidney.

• The cellular composition of a specific lesion can be determined, sometimes beyond its morphological appearance, as in the case of the papillary tumor identified.

• The molecular mechanisms of lesion processes can be identified by comparing lesions at different stages, as in the case of glomerular fibrosis or tubular atrophy.

• To identify potential new genes such as CXCL12 or FXYD5 that may be involved in glomerular fibrosis.

• This method combining traditional histopathology with ST data can pave the way for the future of molecular microscopy and precision pathology.

Lead author Pierre Isnard, MD, PhD, Division of Nephrology, Department of Medicine, and the Department of Developmental Biology, Washington University in St. Louis, concludes, "ST technologies are new and increasingly used in the life sciences, but there is a lack of studies showing their benefits and applications. Here, we demonstrate the complementary nature of these technologies to standard morphological analysis of tissue for identifying, classifying, and understanding lesions. The value of these technologies in healthcare remains to be demonstrated. However, these methods provide a better understanding of the cellular and molecular mechanisms of diseases, which may help identify new biomarkers and/or therapeutic strategies for patients. "

Notes for editors

The article is “Histopathologic Analysis of Human Kidney Spatial Transcriptomics Data: Toward Precision Pathology,” by Pierre Isnard, Dian Li, Qiao Xuanyuan, Haojia Wu, and Benjamin D, Humphreys (https://doi-org.ucc.idm.oclc.org/10.1016/j.ajpath.2024.06.011opens in new tab/window). It appears in The American Journal of Pathology, volume 195, issue 1 (January 2025), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(24)00274-8/fulltextopens in new tab/window.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected]opens in new tab/window to request a PDF of the article or more information. To reach the study’s authors contact Benjamin D. Humphreys, MD, PhD, at [email protected]opens in new tab/window, or Pierre Isnard, MD, PhD, at [email protected]opens in new tab/window.

The study was supported by NIH grants UC2DK126024 and U54DK137332, Assistance Publiquee–Hôpitaux de Paris (France), Philippe Foundation (United States), and Institut Servier Foundation (France).

About The American Journal of Pathology

The American Journal of Pathologyopens in new tab/window, official journal of the American Society for Investigative Pathologyopens in new tab/window, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. https://ajp.amjpathol.orgopens in new tab/window

엘스비어 소개

엘스비어는 첨단 정보와 의사결정 지원 분야의 글로벌 선도 기업으로 100년 넘게 과학과 헬스케어의 발전을 지원하며 인류 진보에 기여해 왔습니다. 우리는 170개국 이상에서 학술 및 기업 연구 커뮤니티, 의사, 간호사, 미래의 의료 전문가와 교육자들을 지원합니다. 근거에 기반한 신뢰할 수 있는 과학·의학 콘텐츠와 최첨단 AI 기술을 결합해 중요한 통찰과 혁신적인 솔루션을 제공해, 의미있는 성과를 이루도록 돕고 있습니다. 또한 다양성과 지속 가능성을 제품과 기업 문화 전반에 내재화하며, 우리가 속한 커뮤니티와 협력합니다. 엘스비어 재단opens in new tab/window은 전 세계에서 연구와 보건 파트너십을 지원합니다.

엘스비어는 전문가 및 기업 고객에게 정보 기반의 분석과 의사결정 도구를 제공하는 글로벌 기업 RELXopens in new tab/window의 일원입니다. 자세한 내용은 www.elsevier.com에서 확인할 수 있으며, 소셜미디어 @elsevierconnect를 통해 최신 소식을 받아보실 수 있습니다.