Single‐cell analysis of MYD88L265P and MYD88WT Waldenström macroglobulinemia patients DOI Creative Commons
Tina Bagratuni, Foteini Aktypi,

Ourania Theologi

et al.

HemaSphere, Journal Year: 2024, Volume and Issue: 8(2)

Published: Feb. 1, 2024

Abstract Waldenström macroglobulinemia (WM) is characterized by the expansion of clonal lymphoplasmacytic cells; MYD88L265P somatic mutation found in >90% patients, but malignant B cells may still display intra‐clonal heterogeneity. To assess heterogeneity WM, we generated and performed single‐cell RNA sequencing CD19 + sorted from five patients with MYD88 L265P two WT genotype as well healthy donors. We identified distinct transcriptional patterns subpopulations not only between genetically WM subgroups also among which affected cell composition different subgroups. Comparison normal/polyclonal within each patient sample enabled identification patient‐specific changes. gene signatures active a subset while other were patients. Finally, expression analysis showed common features compared to control differentially expressed genes involved pathways, including NFκΒ, BCL2, BTK. Overall, our data highlight intra‐tumor potential prognostic therapeutic implications.

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

83

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

64

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

34

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

21

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

17

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

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

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

23

Lymphatic vessels in the age of cancer immunotherapy DOI
Triantafyllia Karakousi, Tenny Mudianto, Amanda W. Lund

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(6), P. 363 - 381

Published: April 11, 2024

Language: Английский

Citations

14