Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217843 - 217843
Published: May 1, 2025
Language: Английский
Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31
Published: Aug. 21, 2024
Language: Английский
Citations
45
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 8, 2025
The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation1. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 neocortical samples encompassing both prefrontal cortex primary visual cortex. These span five main developmental stages, ranging first trimester to adolescence. In parallel, performed spatial transcriptomic analysis on a subset illustrate organization intercellular communication. This atlas enables us catalogue cell-type-specific, age-specific area-specific regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification lineage-tracing experiments, have untangled lineage relationships among subtypes during neurogenesis-to-gliogenesis transition. We identified tripotential intermediate subtype—tripotential cells (Tri-IPCs)—that responsible for local production GABAergic neurons, oligodendrocyte precursor astrocytes. Notably, most glioblastoma resemble Tri-IPCs at level, suggesting that cancer hijack processes enhance growth heterogeneity. Furthermore, integrating our with large-scale genome-wide association study data, created disease-risk map highlighting enriched risk associated autism spectrum disorder in second-trimester intratelencephalic neurons. Our sheds light molecular dynamics developing neocortex. Tripotential are astrocytes
Language: Английский
Citations
11
Science Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 28, 2025
Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on immunocytes guard homeostasis in healthy individuals remains limited. This study highlights heterogeneous, polyfunctional regulatory T cell (T reg ) compartment meninges. A subtype specialized controlling interferon-gamma (IFN-γ) responses another dedicated regulating follicular B were substantial components this compartment. Accordingly, punctual ablation rapidly unleashed IFN-γ production by lymphocytes, unlocked access parenchyma, altered profiles. Distally, hippocampus assumed a reactive state, with morphological transcriptional changes multiple glial types. Within dentate gyrus, neural stem underwent more death blocked from further differentiation, which coincided impairments short-term spatial-reference memory. Thus, regs multifaceted safeguard at steady state.
Language: Английский
Citations
7
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 16, 2024
The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility transcriptome data from 38 neocortical samples encompassing both prefrontal cortex primary visual cortex. These span five main developmental stages, ranging first trimester to adolescence. In parallel, performed spatial transcriptomic analysis on subset illustrate organization intercellular communication. This atlas enables us catalog cell type-, age-, area-specific regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification, lineage-tracing experiments, have untangled lineage relationships among subtypes during transition neurogenesis gliogenesis in neocortex. We identified tripotential intermediate subtype, termed Tri-IPC, responsible for local production GABAergic neurons, oligodendrocyte precursor cells, astrocytes. Remarkably, most glioblastoma cells resemble Tri-IPCs at level, suggesting that cancer hijack processes enhance growth heterogeneity. Furthermore, integrating our with large-scale GWAS data, created disease-risk map highlighting enriched ASD risk second-trimester intratelencephalic projection neurons. Our study sheds light landscape dynamics developing
Language: Английский
Citations
13
Nature Genetics, Journal Year: 2025, Volume and Issue: 57(5), P. 1155 - 1167
Published: May 1, 2025
In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary recurrent GBM samples from 59 patients using single-nucleus RNA sequencing bulk tumor DNA to characterize transcriptional heterogeneity. First, GBMs can be classified by their broad composition, encompassing malignant nonmalignant cell types. Second, in each type describe the diversity of states pathway activation, particularly an expanded set states, including glial progenitor cell-like, neuronal-like cilia-like. Third, remaining variation between highlights three baseline gene expression programs. These layers are interrelated partially associated with specific genetic aberrations, thereby defining stereotypic ecosystems. This work provides unparalleled view multilayered architecture GBM. How this evolves during disease progression is addressed companion manuscript Spitzer et al.
Language: Английский
Citations
2
Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4345 - 4364.e24
Published: Sept. 1, 2023
Progenitor cells are critical in preserving organismal homeostasis, yet their diversity and dynamics the aged brain remain underexplored. We introduced TrackerSci, a single-cell genomic method that combines newborn cell labeling combinatorial indexing to characterize transcriptome chromatin landscape of proliferating progenitor vivo. Using we investigated mouse brains across various ages model Alzheimer's disease. Our dataset revealed diverse types epigenetic signatures. further quantified aging-associated shifts cell-type-specific proliferation differentiation deciphered associated molecular programs. Extending our study human brain, identified conserved genetic signatures species pinpointed region-specific cellular dynamics, such as reduced oligodendrogenesis cerebellum. anticipate TrackerSci will be broadly applicable unveil temporal systems.
Language: Английский
Citations
23
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Feb. 17, 2024
Abstract Abnormal inflammatory states in the brain are associated with a variety of diseases. The dynamic changes number and function immune cells cerebrospinal fluid (CSF) advantageous for early prediction diagnosis diseases affecting brain. aggregated factors inflamed CSF may represent candidate targets therapy. physiological barriers brain, such as blood‒brain barrier (BBB), establish stable environment distribution resident cells. However, underlying mechanism by which peripheral migrate into their role maintaining homeostasis still unclear. To advance our understanding causal link between cell status, we investigated characteristics molecular mechanisms involved common Furthermore, summarized diagnostic treatment methods related cytokines used targets. Further investigations new subtypes contributions to development needed improve specificity
Language: Английский
Citations
7
Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 64 - 64
Published: Jan. 7, 2025
The adult human spinal cord harbors diverse populations of neural stem/progenitor cells (NSPCs) essential for neuroregeneration and central nervous system repair. While induced pluripotent stem cell (iPSC)-derived NSPCs offer significant therapeutic potential, understanding their molecular functional alignment with bona fide is crucial developing autologous therapies that enhance regeneration minimize immune rejection. In this study, we present the first direct transcriptomic comparison syngeneic NSPC populations, including iPSC-derived regionalized to (iPSC-SC) forebrain (iPSC-Br). RNA sequencing analysis revealed distinct profiles disparities among types. iPSC-Br exhibited a close resemblance NSPCs, characterized by enriched expression neurogenesis, axon guidance, synaptic signaling, voltage-gated calcium channel activity pathways. Conversely, iPSC-SC displayed heterogeneity, suboptimal regional specification, elevated crest response-associated genes. Functional assays corroborated findings, demonstrating superior neurogenic potential in NSPCs. Additionally, assessed donor-specific influences on behavior analyzing gene differentiation outcomes across from multiple individuals. Donor-specific factors significantly modulated profiles, notable variability Enrichment pathways related signaling varied donors, highlighting impact genetic epigenetic individuality behavior.
Language: Английский
Citations
1
Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 8, 2025
Language: Английский
Citations
1
Advanced Materials, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 9, 2025
Chiral nanomaterials are widely investigated over recent decades due to their biocompatibility and unique chiral effects. These key properties have significantly promoted the rapid development of in bioengineering medicine. In this review, basic principles constructing along with latest progress research comprehensively summarized. Then, application for diagnosis neurodegenerative diseases (NDDs) is systematically described. addition, significant potential broad prospects treatment NDDs highlighted from several aspects, including disaggregation neurofibrils, scavenging reactive oxygen species, regulation microbial-gut-brain axis, elimination senescent cells, promotion directed differentiation neural stem cells. Finally, a perspective challenges future provided.
Language: Английский
Citations
1