Developmental Cell, Год журнала: 2022, Номер 57(11), С. 1347 - 1368.e12
Опубликована: Май 24, 2022
Язык: Английский
Immunity, Год журнала: 2024, Номер 57(2), С. 379 - 399.e18
Опубликована: Янв. 31, 2024
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas human tonsil composed >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well spatial transcriptomics. This census identified 121 cell types states, defined developmental trajectories, enabled understanding functional units tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer locally active in follicle-associated T B cells, SIX5 putative transcriptional regulator plasma maturation. Analyses validation cohort confirmed presence, annotation, markers tonsillar provided evidence age-related compositional shifts. demonstrate value this resource by annotating from cell-derived mantle lymphomas, linking heterogeneity to normal differentiation states
Язык: Английский
Процитировано
50
Immunity, Год журнала: 2023, Номер 56(7), С. 1631 - 1648.e10
Опубликована: Июнь 30, 2023
CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by and its role in immune surveillance remain unresolved. Using T cell-specific deletion agonist antibodies, we found that modulates tumor infiltration of CD8+-exhausted (Tex) cells expressing PD1, Lag-3, Tim-3 inhibitory receptors. cell-intrinsic, TCR-independent signaling stimulated proliferation terminal differentiation Tex precursor through mechanism involving RelA cRel canonical NF-κB subunits Tox-dependent chromatin remodeling. While cell accumulation induced prophylactic agonists favored growth, anti-PD1 efficacy was improved with subsequent stimulation pre-clinical mouse models. Better understanding exhaustion has crucial implications for treatment infectious diseases. Our results identify as critical regulator expansion holds potential broad therapeutic applications.
Язык: Английский
Процитировано
43
Nature Plants, Год журнала: 2024, Номер 10(2), С. 327 - 343
Опубликована: Янв. 26, 2024
Язык: Английский
Процитировано
37
Developmental Cell, Год журнала: 2024, Номер 59(8), С. 991 - 1009.e12
Опубликована: Март 13, 2024
Язык: Английский
Процитировано
17
Nature Plants, Год журнала: 2025, Номер unknown
Опубликована: Янв. 3, 2025
Язык: Английский
Процитировано
3
Science Advances, Год журнала: 2025, Номер 11(8)
Опубликована: Фев. 19, 2025
The steroidal glycoalkaloids (SGAs) produced in Solanaceae crops, including tomato, are antinutritional because of their cellular toxicity and resultant bitter taste to humans. To make fruits palatable, SGA profiles shift from toxic α-tomatine nonbitter nontoxic esculeoside A during the ripening process. However, mechanisms regulating this conversion remain unclear. In study, we showed that removal SGAs is under control DNA demethylation, ethylene, key transcription factors by forming a feedback loop governs expression GLYCOALKALOID METABOLISM ( GAME ) genes ripening. Moreover, ethylene-inducible NON-RIPENING, RIPENING INHIBITOR, FRUITFULL1 coordinately regulate GAME31 , GAME40 GAME5 glycoalkaloid transporter gene GORKY whereas jasmonic acid–induced MYC2 modulates GAME36 . Furthermore, demethylation mediated DEMETER - LIKE 2 drives detoxification tomato domestication.
Язык: Английский
Процитировано
3
PLANT PHYSIOLOGY, Год журнала: 2021, Номер 188(1), С. 425 - 441
Опубликована: Ноя. 2, 2021
Abstract Highly efficient tissue repair is pivotal for surviving damage-associated stress. Plants generate callus upon injury to heal wound sites, yet regulatory mechanisms of remain elusive. Here, we identified WUSCHEL-RELATED HOMEOBOX 13 (WOX13) as a key regulator formation and organ adhesion in Arabidopsis (Arabidopsis thaliana). WOX13 belongs an ancient subclade the WOX family, previous study shows that orthologs moss Physcomitrium patens (PpWOX13L) are involved cellular reprogramming at sites. We found wox13 mutant totally defective establishing reconnection grafting, suggesting crucial seed plants. expression rapidly induced wounding, which was partly dependent on activity AP2/ERF transcription factor, WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1). turn directly upregulated WIND2 WIND3 further promote regeneration. also orchestrates transcriptional induction cell wall-modifying enzyme genes, such GLYCOSYL HYDROLASE 9Bs, PECTATE LYASE LIKEs EXPANSINs. Furthermore, chemical composition wall monosaccharides markedly different mutant. These data together suggest modifies properties, may facilitate reconnection. PpWOX13L complements mutant, molecular function conserved between mosses This provides insights into conservation functional diversification gene family during land plant evolution.
Язык: Английский
Процитировано
103
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Июль 23, 2022
Mutations in genes that confer a selective advantage to hematopoietic stem cells (HSCs) drive clonal hematopoiesis (CH). While some CH drivers have been identified, the compendium of all able upon mutations HSCs remains incomplete. Exploiting signals positive selection blood somatic may be an effective way identify driver genes, analogously cancer. Using tumor sample blood/tumor pairs as reference, we across more than 12,000 donors from two large cancer genomics cohorts. The application IntOGen, discovery pipeline, both cohorts, and 24,000 targeted sequenced samples yields list close 70 with CH, available at http://www.intogen.org/ch . This approach recovers known discovers other candidates.
Язык: Английский
Процитировано
66
Molecular Systems Biology, Год журнала: 2021, Номер 17(9)
Опубликована: Сен. 1, 2021
Язык: Английский
Процитировано
64
Nature Genetics, Год журнала: 2022, Номер 54(8), С. 1133 - 1144
Опубликована: Июль 11, 2022
Язык: Английский
Процитировано
64