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Conventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular dynamics in the mammalian brain. Profiling approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles across diverse mouse brains, we identified over 300 cell subtypes, uncovering their molecular characteristics and spatial locations. This comprehensive view elucidates rare cell types expanded or depleted upon aging. We also investigated cell-type-specific responses to genetic alterations linked to Alzheimer's disease, identifying associated rare cell types. Additionally, by profiling 118,240 human brain single-cell transcriptomes, we discerned cell- and region-specific transcriptomic changes tied to Alzheimer's pathogenesis. In conclusion, this research offers a valuable resource for probing cell-type-specific dynamics in both normal and pathological aging.
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http://dx.doi.org/10.1038/s41588-023-01572-y | DOI Listing |
Pathol Res Pract
September 2025
Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address:
Background: Dermal clear cell sarcoma (DCCS) is a rare malignant mesenchymal neoplasm. Owing to the overlaps in its morphological and immunophenotypic profiles with a broad spectrum of tumors exhibiting melanocytic differentiation, it is frequently misdiagnosed as other tumor entities in clinical practice. By systematically analyzing the clinicopathological characteristics, immunophenotypic features, and molecular biological properties of DCCS, this study intends to further enhance pathologists' understanding of this disease and provide a valuable reference for its accurate diagnosis.
View Article and Find Full Text PDFJCO Precis Oncol
September 2025
Division of Hematology and Oncology, University of California Los Angeles, Los Angeles, CA.
Purpose: mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with -mutated NSCLC. The real-world prevalence of -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic mutations in ovarian cancer and describe a case of -mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy.
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
Division of Applied Mathematics, Brown University, Providence, Rhode Island, United States of America.
Gaucher Disease (GD) is a rare genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucosylceramide in various cells, including red blood cells (RBCs). This accumulation results in altered biomechanical properties and rheological behavior of RBCs, which may play an important role in blood rheology and the development of bone infarcts, avascular necrosis (AVN) and other bone diseases associated with GD. In this study, dissipative particle dynamics (DPD) simulations are employed to investigate the biomechanics and rheology of blood and RBCs in GD under various flow conditions.
View Article and Find Full Text PDFSci Transl Med
September 2025
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are essential for the formation of myelin sheaths and pivotal for maintaining axonal integrity and conduction. Disruption of these cells and the myelin sheaths they produce is a hallmark of demyelinating conditions like multiple sclerosis or those resulting from certain drug side effects, leading to profound neurological impairments. In this study, we created a human brain organoid comprising neurons, astrocytes, and myelinating oligodendrocytes.
View Article and Find Full Text PDFAnticancer Drugs
September 2025
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain.
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