Exploring Lymph Node Stroma Ageing: Immune Implications and Future Directions DOI Creative Commons
Yu Yang Ng, Andy Tay

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Ageing is an inevitable biological process that impacts the immune system, leading to immunosenescence and inflammaging, which contribute increased susceptibility infections, autoimmune diseases cancers in individuals over age of 65. This review focuses on ageing lymph node stromal cells (LNSCs), are crucial for maintaining (LN) structure function. Age-related changes LNs, such as fibrosis lipomatosis, disrupt LN architecture reduce cell recruitment function, impairing responses infections vaccinations. The discusses structural functional decline various LNSC subsets, including fibroblastic reticular (FRCs), lymphatic endothelial (LECs) blood (BECs), highlighting their roles activation homeostasis. Potential strategies restore aged enhancing during vaccination using senotherapeutics, explored. Outstanding questions regarding mechanisms how stroma might impact disorders also addressed. aims stimulate further research into characterisation LNSCs development therapeutic interventions improve function older adults.

Language: Английский

Cell type-specific inference of differential expression in spatial transcriptomics DOI
Dylan Cable, Evan Murray, Vignesh Shanmugam

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(9), P. 1076 - 1087

Published: Sept. 1, 2022

Language: Английский

Citations

93
Advances in single-cell RNA sequencing and its applications in cancer research DOI Creative Commons
Dezhi Huang,

Naya Ma,

Xinlei Li

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 24, 2023

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition functional capabilities during transition from normal to neoplastic state. Powerful experimental and computational tools can be applied elucidate mechanisms occurrence, progression, metastasis, drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect average gene expression in sample, making it difficult understand tumor heterogeneity microenvironment. The emergence development single-cell (scRNA-seq) technologies have provided opportunities subtle changes biology identifying distinct cell subpopulations, dissecting microenvironment, characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used cancer studies explore which increased understanding tumorigenesis evolution. This review summarizes basic processes their increasing applications research clinical practice.

Language: Английский

Citations

86
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage DOI Creative Commons
Jin‐Hui Yoon, Hokyung Jin, Hae Jin Kim

et al.

Nature, Journal Year: 2024, Volume and Issue: 625(7996), P. 768 - 777

Published: Jan. 10, 2024

Cerebrospinal fluid (CSF) in the subarachnoid space around brain has long been known to drain through lymphatics cervical lymph nodes

Language: Английский

Citations

72
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics DOI
Gunsagar S. Gulati,

Jeremy Philip D’Silva,

Yunhe Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31

Published: Aug. 21, 2024

Language: Английский

Citations

37
Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients DOI
Andrea J. Radtke, Ekaterina Postovalova, Arina Varlamova

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 444 - 463.e10

Published: Feb. 29, 2024

Language: Английский

Citations

22
Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity DOI
Ateeq Khaliq, Meenakshi Rajamohan, Omer Saeed

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(11), P. 2455 - 2465

Published: Sept. 18, 2024

Language: Английский

Citations

18
Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma DOI Creative Commons
Benedetta Apollonio, Filomena Spada, Nedyalko Petrov

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(13)

Published: May 23, 2023

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance lymph node (LN) fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within tumor microenvironment (TME). However, immunomodulatory role fibroblasts in remains unclear. Here, by studying human mouse DLBCL-LNs, we identify presence an aberrantly remodeled fibroblastic reticular (FRC) network, expressing elevated activated protein (FAP). RNA-sequencing analyses reveal that exposure to DLBCL reprograms key immunoregulatory pathways FRCs, including a switch from homeostatic inflammatory chemokine expression antigen presentation molecules. Functional assays show DLBCL-activated FRCs (DLBCL-FRCs) hinder optimal TIL chimeric receptor T (CAR-T) migration. Moreover, DLBCL-FRCs inhibited CD8+ cytotoxicity antigen-specific manner. Notably, interrogation patient LNs with imaging mass cytometry identified distinct environments differing their TIL-FRC composition spatial organization associated survival outcomes. We further demonstrate potential target inhibitory rejuvenate interacting TILs. Co-treating organotypic cultures FAP-targeted immunostimulatory drugs bispecific antibody (glofitamab) augmented anti-lymphoma cytotoxicity. Together, our study reveals immunosuppressive DLBCL, implications for immune evasion, disease pathogenesis optimizing immunotherapy patients.

Language: Английский

Citations

32
Single-cell RNA sequencing reveals the developmental program underlying proximal–distal patterning of the human lung at the embryonic stage DOI Creative Commons
Shangtao Cao, Huijian Feng,

Hongyan Yi

et al.

Cell Research, Journal Year: 2023, Volume and Issue: 33(6), P. 421 - 433

Published: April 21, 2023

Abstract The lung is the primary respiratory organ in human, which proximal airway and distal alveoli are responsible for air conduction gas exchange, respectively. However, regulation of proximal–distal patterning at embryonic stage human development largely unknown. Here we investigated early embryos weeks 4–8 post fertilization (Carnegie stages 12–21) using single-cell RNA sequencing, obtained a transcriptomic atlas 169,686 cells. We observed discernible gene expression patterns epithelia week 4, upon initiation organogenesis. Moreover, identified novel transcriptional regulators (e.g., THRB EGR3) ETV1 SOX6) epithelia. Further dissection revealed various stromal cell populations, including an early-embryonic BDNF + population, providing niche with spatial specificity. In addition, elucidated fate bifurcation maturation vascular smooth muscle progenitor cells development. Together, our study expands scope developmental biology stages. discovery intrinsic providers deepens understanding epithelial development, opening up new avenues regenerative medicine.

Language: Английский

Citations

31
New tools for immunologists: models of lymph node function from cells to tissues DOI Creative Commons
Tochukwu Ozulumba,

Alyssa N. Montalbine,

Jennifer E. Ortiz-Cárdenas

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

The lymph node is a highly structured organ that mediates the body’s adaptive immune response to antigens and other foreign particles. Central its function distinct spatial assortment of lymphocytes stromal cells, as well chemokines drive signaling cascades which underpin responses. Investigations biology were historically explored in vivo animal models, using technologies breakthroughs their time such immunofluorescence with monoclonal antibodies, genetic reporters, two-photon imaging, and, more recently techniques. However, new approaches are needed enable tests cell behavior spatiotemporal dynamics under controlled experimental perturbation, particularly for human immunity. This review presents suite technologies, comprising vitro, ex silico developed study or components. We discuss use these tools model behaviors increasing order complexity, from motility, cell-cell interactions, organ-level functions vaccination. Next, we identify current challenges regarding sourcing culture, real measurements tool development analysis control engineered cultures. Finally, propose research directions offer our perspective on future this rapidly growing field. anticipate will be especially beneficial immunologists looking expand toolkit probing structure function.

Language: Английский

Citations

24
Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics DOI Creative Commons

Anqi Liang,

Ying Kong, Zhi Hong Chen

et al.

Biochemistry and Biophysics Reports, Journal Year: 2023, Volume and Issue: 37, P. 101589 - 101589

Published: Nov. 29, 2023

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of together, single-cell enables uncover the heterogeneity within tumors and understand unique characteristics different cell populations. By doing so, we can identify rare subpopulations that are influential in tumor growth, metastasis, resistance therapy. Moreover, analysis provides valuable insights into immune response triggered various therapeutic interventions, such as checkpoint blockade, chemotherapy, It also helps better intricate microenvironment its impact on patient prognosis treatment. This comprehensive review focuses recent advancements methodologies, with an emphasis technologies. highlights important role these techniques uncovering complexity tumorigenesis multiple applications research, well their equally great contributions other areas immunology. Through multi-omics, gain deeper understanding biology pave way for more precise effective strategies. Apart from those above, this paper aims introduce live imaging technology, latest developments protein detection techniques, explore seamless integration technology.

Language: Английский

Citations

24