ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses DOI Creative Commons
Irem Kaymak, McLane J. Watson, Brandon M. Oswald

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(9)

Published: July 4, 2024

Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an metabolic node CD8 function in vivo. We show that responses to infection depend on derived from citrate via the enzyme ATP lyase (ACLY). However, ablation ACLY triggers alternative, acetate-dependent pathway mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2). Mechanistically, acetate fuels both TCA cycle and production, impacting effector responses, histone acetylation, chromatin accessibility at gene loci. When functional, ACSS2 not required, suggesting obligate substrate function. loss renders cells dependent (via ACSS2) maintain Together, coordinate

Language: Английский

Strategies for non-viral vectors targeting organs beyond the liver DOI
Jeonghwan Kim, Yulia Eygeris, Renee C. Ryals

et al.

Nature Nanotechnology, Journal Year: 2023, Volume and Issue: 19(4), P. 428 - 447

Published: Dec. 27, 2023

Language: Английский

Citations

60
Tracking chromatin state changes using nanoscale photo-proximity labelling DOI
Ciaran P. Seath, Antony J. Burton,

Xuemeng Sun

et al.

Nature, Journal Year: 2023, Volume and Issue: 616(7957), P. 574 - 580

Published: April 5, 2023

Language: Английский

Citations

59
Decoding the genetic and epigenetic basis of asthma DOI Creative Commons
Bernard Stikker, Rudi W. Hendriks, Ralph Stadhouders

et al.

Allergy, Journal Year: 2023, Volume and Issue: 78(4), P. 940 - 956

Published: Feb. 2, 2023

Abstract Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility strongly influenced by genetics. Given its high prevalence our incomplete understanding mechanisms underlying susceptibility, frequently studied in genome‐wide association studies (GWAS), which have identified thousands genetic variants associated with development. Virtually all these reside non‐coding genomic regions, has obscured functional impact asthma‐associated their translation into disease‐relevant mechanisms. Recent advances genomics technology epigenetics now offer methods to link gene regulatory elements embedded within started unravel molecular (epi)genetics asthma. Here, we provide an integrated overview (epi)genetic asthma, focusing on efforts associations biological insight pathophysiology using state‐of‐the‐art methodology. Finally, perspective as how decoding epigenetic basis potential transform clinical management predict risk

Language: Английский

Citations

48
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

26
Genetic variation across and within individuals DOI
Zhi Yu, Tim H. H. Coorens, Md Mesbah Uddin

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(8), P. 548 - 562

Published: March 28, 2024

Language: Английский

Citations

25
Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes DOI
Úrzula Franco‐Enzástiga,

Nikhil Nageshwar Inturi,

Keerthana Natarajan

et al.

Pain, Journal Year: 2025, Volume and Issue: 166(3), P. 614 - 630

Published: Jan. 23, 2025

Abstract Cell states are influenced by the regulation of gene expression orchestrated transcription factors capable binding to accessible DNA regions. To uncover if sex differences exist in chromatin accessibility human dorsal root ganglion (hDRG), where nociceptive neurons innervating body found, we performed bulk and spatial assays for transposase-accessible technology followed sequencing (ATAC-seq) from organ donors without a history chronic pain. Using ATAC-seq, detected abundant hDRG. In women, differentially regions (DARs) mapped mostly X chromosome, whereas men, they autosomal genes. Hormone-responsive factor motifs such as EGR1/3 were within DARs while JUN, FOS, other activating protein 1 enriched suggesting higher activation state cells compared with women. These observations consistent ATAC-seq data. Furthermore, validated that EGR1 is biased female hDRG using RNAscope. neurons, revealed GABAergic, glutamatergic, interferon-related genes women Ca 2+ -signaling-related men. Strikingly, XIST, responsible inactivating chromosome compacting it maintaining at periphery nucleus, was found be highly dispersed neuronal nuclei. This likely related observed both approaches. We have documented baseline epigenomic which provide important descriptive information test future hypotheses.

Language: Английский

Citations

4
Global identification of SWI/SNF targets reveals compensation by EP400 DOI Creative Commons
Benjamín Martín, Eileen F. Ablondi, Christine Goglia

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(24), P. 5290 - 5307.e26

Published: Nov. 1, 2023

Language: Английский

Citations

39
Integrating omics databases for enhanced crop breeding DOI Creative Commons
Haoyu Chao, Shilong Zhang, Yueming Hu

et al.

Berichte aus der medizinischen Informatik und Bioinformatik/Journal of integrative bioinformatics, Journal Year: 2023, Volume and Issue: 20(4)

Published: July 24, 2023

Abstract Crop plant breeding involves selecting and developing new varieties with desirable traits such as increased yield, improved disease resistance, enhanced nutritional value. With the development of high-throughput technologies, genomics, transcriptomics, metabolomics, crop has entered a era. However, to effectively use these integration multi-omics data from different databases is required. Integration omics provides comprehensive understanding biological processes underlying their interactions. This review highlights importance integrating in breeding, discusses available databases, describes challenges, recent developments potential benefits. Taken together, critical step towards enhancing improving global food security.

Language: Английский

Citations

29
Next-Generation sequencing transforming clinical practice and precision medicine DOI
Deepali Yadav, Bhagyashri Patil‐Takbhate, Anil S. Khandagale

et al.

Clinica Chimica Acta, Journal Year: 2023, Volume and Issue: 551, P. 117568 - 117568

Published: Oct. 13, 2023

Language: Английский

Citations

29
Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system DOI Creative Commons
Lillian Campos, Cynthia M. Arokiaraj, Miguel R. Chuapoco

et al.

Current Research in Neurobiology, Journal Year: 2023, Volume and Issue: 4, P. 100086 - 100086

Published: Jan. 1, 2023

Modern neuroscience approaches including optogenetics, calcium imaging, and other genetic manipulations have facilitated our ability to dissect specific circuits in rodent models study their role neurological disease. These regularly use viral vectors deliver cargo (e.g., opsins) tissues genetically-engineered rodents achieve cell-type specificity. However, the translatability of these models, cross-species validation identified targets, translational efficacy potential therapeutics larger animal like nonhuman primates remains difficult due lack efficient primate vectors. A refined understanding nervous system promises insights that can guide development treatments for neurodegenerative diseases. Here, we outline recent advances adeno-associated optimized primates. tools promise help open new avenues further brain.

Language: Английский

Citations

25