Subcellular Proteomic Mapping of Lysine Lactylation DOI

Qiuyu Bao,

Ning Wan,

Zimeng He

et al.

Journal of the American Society for Mass Spectrometry, Journal Year: 2024, Volume and Issue: 35(12), P. 3221 - 3232

Published: Nov. 21, 2024

Protein lactylation is a novel post-translational modification (PTM) involved in many important physiological processes such as macrophage polarization, immune regulation, and tumor cell growth. However, traditional methodologies for studying have predominantly relied on peptide enrichment from whole-cell lysates, which tend to favor the detection of high-abundance peptides, thus limiting identification low-abundance lactylated peptides. To address this limitation, here, we employed subcellular fractionation separate proteins map peptides each isolated fraction using model line. In brief, identified 1,217 lysine (Kla) sites 553 across four fractions. Subsequent pathway analysis revealed that Kla participate distinct pathways depending contexts. addition, method enabled discovery 36 previously unreported 223 sites, are present low abundance. Notably, several contain multiple newly exemplified by transcriptional regulator ATRX. Furthermore, our results indicate possibility PTM crosstalk between other PTMs ubiquitination sumoylation. conclusion, facilitates been uncovered could be overlooked affinity lysates.

Language: Английский

The molecular basis of heterochromatin assembly and epigenetic inheritance DOI Creative Commons
Shiv I. S. Grewal

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(11), P. 1767 - 1785

Published: May 18, 2023

Language: Английский

Citations

103
Aging activates escape of the silent X chromosome in the female mouse hippocampus DOI Creative Commons
Margaret Gadek, Cayce K. Shaw, Samira Abdulai-Saiku

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(10)

Published: March 5, 2025

Women live longer than men and exhibit less cognitive aging. The X chromosome contributes to sex differences, as females harbor an inactive (Xi) active (Xa), in contrast males with only Xa. Thus, reactivation of silent Xi genes may contribute differences. We use allele-specific, single-nucleus RNA sequencing show that aging remodels transcription the Xa across hippocampal cell types. Aging preferentially changed gene expression on X's relative autosomes. Select underwent activation, new escape cells including dentate gyrus, critical learning memory. Expression escapee Plp1, a myelin component, was increased hippocampus female mice parahippocampus women. AAV-mediated Plp1 elevation gyrus male improved cognition. Understanding how confer advantage could lead novel targets counter brain disease both sexes.

Language: Английский

Citations

8
Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice DOI Creative Commons
Mary E. Fuentes, Xiaoyin Lu, Natasha Flores

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 12, 2024

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of that exhibit an unpredictable and broad spectrum clinical presentations biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but majority patients diagnosed at advanced metastatic stage with limited options. Key factors limiting development new therapeutics extensive heterogeneity PanNETs lack appropriate clinically relevant models. In context, genomic sequencing human revealed recurrent mutations structural alterations in several tumor suppressors. Here, we demonstrated combined loss MEN1, ATRX, PTEN, suppressors commonly mutated PanNETs, triggers high-grade pancreatic mice. Histopathological evaluation gene expression analyses developed confirm presence PanNET hallmarks significant overlap patterns found disease. Thus, postulate presented novel genetically defined mouse model first immunocompetent model.

Language: Английский

Citations

12
A single-cell atlas of the Culex tarsalis midgut during West Nile virus infection DOI Creative Commons
Emily Fitzmeyer, Taru S. Dutt, Silvain Pinaud

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012855 - e1012855

Published: Jan. 27, 2025

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of physiology virus infection dynamics are scarce, in Culex tarsalis— an extremely efficient vector West Nile (WNV) — nonexistent. We performed single-cell RNA sequencing on Cx. tarsalis midguts, defined multiple cell types, determined whether specific types more permissive to WNV infection. identified 20 states comprising 8 distinct consistent with existing descriptions Drosophila Aedes aegypti physiology. Most populations were there higher levels (vRNA) enteroendocrine cells, suggesting enhanced replication this population. In contrast, proliferating intestinal stem cells (ISC) had the lowest vRNA, finding ISC proliferation is involved control. ISCs also found have strong transcriptional response infection; genes ribosome structure biogenesis, translation significantly downregulated WNV-infected populations. Notably, we did not detect significant WNV-infection induced upregulation canonical antiviral immune (e.g., AGO2 , R2D2 etc.) at whole-midgut level. Rather, observed positive correlation gene expression vRNA load individual that within high may trigger responses. Our findings establish atlas, provide insight into by characterizing cell-type enhancement/restriction of, to,

Language: Английский

Citations

1
ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma. DOI
Federica Lorenzi, Sina Jostes, Qiong Gao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217495 - 217495

Published: Jan. 1, 2025

Language: Английский

Citations

1
HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape DOI Creative Commons
Jinmi Choi, Tae‐Wan Kim, Eun‐Jung Cho

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(2), P. 251 - 263

Published: Feb. 1, 2024

Abstract H3.3, the most common replacement variant for histone H3, has emerged as an important player in chromatin dynamics controlling gene expression and genome integrity. While replicative variants H3.1 H3.2 are primarily incorporated into nucleosomes during DNA synthesis, H3.3 is under control of H3.3-specific chaperones spatiotemporal incorporation throughout cell cycle. Over years, there been progress understanding mechanisms by which affects domain structure function. Furthermore, distribution relative abundance profoundly impact cellular identity plasticity normal development pathogenesis. Recurrent mutations its have identified neoplastic transformation developmental disorders, providing new insights biology disease. Here, we review recent findings emphasizing how two distinct chaperones, HIRA DAXX, take part spatial temporal different domains ultimately achieve dynamic organization Elucidating deposition pathways from available pool will open avenues epigenetically regulates on integrity

Language: Английский

Citations

7
Germline structural variation globally impacts the cancer transcriptome including disease-relevant genes DOI Creative Commons
Fengju Chen, Yiqun Zhang, Fritz J. Sedlazeck

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(3), P. 101446 - 101446

Published: March 1, 2024

Germline variation and somatic alterations contribute to the molecular profile of cancers. We combine RNA with whole genome sequencing across 1,218 cancer patients determine extent germline structural variants (SVs) impact expression nearby genes. For hundreds genes, recurrent common SV breakpoints within 100 kb associate increased or decreased in tumors spanning various tissues origin. A significant fraction associations involves duplication intergenic enhancers 3′ UTR disruption. Genes altered by both SVs include ATRX CEBPA. essential cell lines BARD1 IRS2. breakpoint patterns associated patient survival GCLM. Our results capture a class phenotypic at work disease setting, including genes roles. Specific represent potential risk for genetic testing, those involving targeting implications.

Language: Английский

Citations

3
SARS-CoV-2 disrupts host gene networks: Unveiling key hub genes as potential therapeutic targets for COVID-19 management DOI Creative Commons
Marta Majewska, Mateusz Maździarz, Katarzyna Krawczyk

et al.

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 183, P. 109343 - 109343

Published: Nov. 4, 2024

Language: Английский

Citations

3
A Long-term Progression-free Survival with Glioblastoma Patient Harboring MSH6 Pathogenic Germline Mutation: A Case Report DOI Creative Commons
Yiqiang Zhou,

Yanxiang Zhang,

Tiantian Han

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Background Lynch syndrome (LS) is a cancer caused by germline mutations in DNA mismatch repair genes. Patients with have higher risk of brain tumors, predominantly high-grade gliomas. LS-related gliomas poor overall survival. Case presentation We present case a31-year-old male patient frontal lesion magnetic resonance imaging (MRI). The pathological diagnosis was isocitrate dehydrogenase (IDH)wildtype glioblastoma (WHO grade 4) 30% Ki-67 proliferation index. After surgery, this received radiotherapy and temozolomide chemotherapy following Stupp protocol. During over 64 months follow up, no sign tumor recurrence found after surgery. Therefore, next-generation sequencing suggested to patient. result revealed heterozygous variation c.3261dup exon 5 MSH6 gene which resulted truncated MSH6 protein (MSH6 p.F1088Lfs*5) mutation burden 327.36 Mut/Mb. Conclusion MMR deficiency may lead TMZ resistance glioma cells. However, had long-term benefits from standard radio- chemo-therapy probably due the distinct molecular characteristics microenvironment. This finding provided insight perform clinical studies investigate characterization associated patients role microglia antitumor.

Language: Английский

Citations

0
Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma DOI Creative Commons

Albatool AlKhazal,

Saibah Chohan,

David J. Ross

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 4, 2025

Neuroblastoma is a pediatric cancer that originates from neural crest cells and the most common extracranial solid tumor in children under five years of age. While low-risk neuroblastoma often regresses spontaneously, high-risk poses significant clinical challenge. Recent advances understanding neuroblastoma’s molecular mechanisms have led to development targeted therapies aim selectively inhibit specific pathways involved growth progression, improving patient outcomes while minimizing side effects. This review provides comprehensive biology emerging therapeutic strategies. Key topics include (a) immunotherapies immunotargets, (b) non-coding RNAs (long RNA, microRNA, circular RNA), (c) biomarkers pathways, (d) limitations future directions.

Language: Английский

Citations

0