N6-methyladenosine (m6A) in cancer stem cell: From molecular mechanisms to therapeutic implications DOI Creative Commons
Liming Wang,

Yuanxin Tang

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 163, С. 114846 - 114846

Опубликована: Май 9, 2023

The emergence of drug resistance and metastasis has long been a difficult problem for cancer treatment. Recent studies have shown that stem cell populations are key factors in the regulation aggressiveness, relapse resistance. Cancer (CSC) highly plastic self-renewing, giving them unique metabolic, metastatic, chemotherapy properties. N6-methyladenosine (m6A) is most abundant internal modification mRNA involved variety growth development processes, including RNA transcription, alternative splicing, degradation, translation. It also linked to various cancers. At present, important role m6A tumour progression gradually attracting attention, especially stemness process. Abnormal modifications regulate metastasis, recurrence This paper aims explore regulatory mechanism CSCs clinical therapy, clarify its network, provide theoretical guidance targets improvement therapeutic effects.

Язык: Английский

Spatial biology of cancer evolution DOI
Zaira Seferbekova, Artem Lomakin, Lucy Yates

и другие.

Nature Reviews Genetics, Год журнала: 2022, Номер 24(5), С. 295 - 313

Опубликована: Дек. 9, 2022

Язык: Английский

Процитировано

117
Spatial transcriptomics: Technologies, applications and experimental considerations DOI Creative Commons
Ye Wang, Bin Liu, Gexin Zhao

и другие.

Genomics, Год журнала: 2023, Номер 115(5), С. 110671 - 110671

Опубликована: Июнь 21, 2023

The diverse cell types of an organ have a highly structured organization to enable their efficient and correct function. To fully appreciate gene functions in given type, one needs understand how much, when where the is expressed. Classic bulk RNA sequencing popular single destroy structural fail provide spatial information. However, location expression or complex tissue provides key clues comprehend neighboring genes cells cross talk, transduce signals work together as team complete job. functional requirement for content has been driving force rapid development transcriptomics technologies past few years. Here, we present overview current with special focus on commercially available currently being commercialized technologies, highlight applications by category discuss experimental considerations first experiment.

Язык: Английский

Процитировано

78
The co-evolution of the genome and epigenome in colorectal cancer DOI Creative Commons
Timon Heide, Jacob Househam, George D. Cresswell

и другие.

Nature, Год журнала: 2022, Номер 611(7937), С. 733 - 743

Опубликована: Окт. 26, 2022

Abstract Colorectal malignancies are a leading cause of cancer-related death 1 and have undergone extensive genomic study 2,3 . However, DNA mutations alone do not fully explain malignant transformation 4–7 Here we investigate the co-evolution genome epigenome colorectal tumours at single-clone resolution using spatial multi-omic profiling individual glands. We collected 1,370 samples from 30 primary cancers 8 concomitant adenomas generated 1,207 chromatin accessibility profiles, 527 whole genomes 297 transcriptomes. found positive selection for in modifier genes recurrent somatic alterations, including regulatory regions cancer driver that were otherwise devoid genetic mutations. Genome-wide alterations transcription factor binding involved CTCF, downregulation interferon increased SOX HOX families, suggesting involvement developmental during tumourigenesis. Somatic heritable distinguished cancers. Mutational signature analysis showed turn influences accumulation This provides map epigenetic tumour heterogeneity, with fundamental implications understanding biology.

Язык: Английский

Процитировано

75
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics DOI
Gunsagar S. Gulati,

Jeremy Philip D’Silva,

Yunhe Liu

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 26(1), С. 11 - 31

Опубликована: Авг. 21, 2024

Язык: Английский

Процитировано

31
Mechanisms of metastatic colorectal cancer DOI
Adrià Cañellas‐Socias, Elena Sancho, Eduard Batlle

и другие.

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2024, Номер 21(9), С. 609 - 625

Опубликована: Май 28, 2024

Язык: Английский

Процитировано

30
Mapping single-cell developmental potential in health and disease with interpretable deep learning DOI Open Access
Minji Kang, José Juan Almagro Armenteros, Gunsagar S. Gulati

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 21, 2024

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cell fate in developmental systems. However, identifying the molecular hallmarks potency - capacity a to differentiate into other types remained challenging. Here, we introduce CytoTRACE 2, an interpretable deep learning framework for characterizing and differentiation states on absolute scale from scRNA-seq data. Across 31 human mouse datasets encompassing 28 tissue types, 2 outperformed existing methods recovering experimentally determined levels covering entire range cellular ontogeny. Moreover, it reconstructed temporal hierarchy embryogenesis across 62 timepoints; identified pan-tissue expression programs that discriminate major levels; facilitated discovery phenotypes cancer linked survival immunotherapy resistance. Our results illuminate fundamental feature biology provide broadly applicable platform delineating single-cell landscapes health disease.

Язык: Английский

Процитировано

24
Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors DOI Creative Commons
Cody N. Heiser, Alan J. Simmons,

Frank Revetta

и другие.

Cell, Год журнала: 2023, Номер 186(25), С. 5620 - 5637.e16

Опубликована: Дек. 1, 2023

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data 31 human colorectal specimens enabled phylogeographic mapping tumor evolution that revealed individualized trajectories accompanying microenvironmental clonal alterations. Phylogeographic ordered events, classified tumors by their evolutionary dynamics, placed regions along global pseudotemporal encompassing the chromosomal instability (CIN+) hypermutated (HM) pathways. Integrated single-cell transcriptomic recurring epithelial programs infiltrating immune states pseudotime. We discovered an exclusion signature (IEX), consisting extracellular matrix regulators DDR1, TGFBI, PAK4, DPEP1, charts with CIN+ progression, is associated reduced cytotoxic cell infiltration, shows prognostic value in independent cohorts. This atlas provides insights into tumor-microenvironment co-evolution, serving as a resource for stratification targeted treatments.

Язык: Английский

Процитировано

39
Trellis tree-based analysis reveals stromal regulation of patient-derived organoid drug responses DOI Creative Commons
María Ramos Zapatero, Alexander Tong, James W. Opzoomer

и другие.

Cell, Год журнала: 2023, Номер 186(25), С. 5606 - 5619.e24

Опубликована: Дек. 1, 2023

Patient-derived organoids (PDOs) can model personalized therapy responses; however, current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly multiplexed mass cytometry platform to measure post-translational modification (PTM) signaling, DNA damage, cell-cycle activity, and apoptosis in >2,500 colorectal cancer (CRC) PDOs cancer-associated fibroblasts (CAFs) clinical therapies at single-cell resolution. compare patient- microenvironment-specific responses thousands of datasets, "Trellis"-a scalable, tree-based treatment effect analysis method. Trellis revealed that on-target blockage DNA-damage effects are common, even chemorefractory PDOs. However, drug-induced is rarer, patient-specific, aligns with cell PTM signaling. We find CAFs regulate PDO plasticity-shifting proliferative colonic stem (proCSCs) slow-cycling revival (revCSCs) protect from chemotherapy.

Язык: Английский

Процитировано

35
State-dependent evolutionary models reveal modes of solid tumour growth DOI Creative Commons
Maya A. Lewinsohn, Trevor Bedford, Nicola F. Müller

и другие.

Nature Ecology & Evolution, Год журнала: 2023, Номер 7(4), С. 581 - 596

Опубликована: Март 9, 2023

Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster on the periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively acquire mutations than slower-dividing centre lineages. We develop Bayesian state-dependent evolutionary phylodynamic model (SDevo) quantifies these patterns infer differential rates between central this approach accurately infers varying birth simulated tumours across range conditions sampling strategies. then show SDevo outperforms state-of-the-art, non-cancer multi-state methods ignore sequence evolution. Finally, apply single-time-point, multi-region sequencing data hepatocellular carcinomas find evidence three- six-times-higher rate edge. With increasing availability high-resolution, sequencing, anticipate will be useful interrogating restrictions could extended non-spatial factors influence progression.

Язык: Английский

Процитировано

29
Contribution of pks+ E. coli mutations to colorectal carcinogenesis DOI Creative Commons
Bingjie Chen, Daniele Ramazzotti, Timon Heide

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 29, 2023

Abstract The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, a small subgroup, mismatch repair signatures 6 and 44). Mutations common driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from patients, matched to previous multi-omic tumour dataset. We analyse that were distant vs adjacent the cancer. In contrast healthy individuals, patients have high incidence pks + (polyketide synthases) E.coli ( Escherichia coli ) indel signatures, this confirmed by metagenomics. These compatible many clonal mutations detected corresponding samples, including chromatin modifier genes, supporting their role early tumourigenesis. results provide evidence potential carcinogenesis human gut.

Язык: Английский

Процитировано

27