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Biology subjects

Pham, G.

Publications and source records attributed to Pham, G..

2 recordsLinked to original sources

The control of prickle formation in Rubus

Prickles on blackberry and raspberry canes make pruning, harvesting, and handling more difficult and can increase labor costs for growers. The trait has been challenging to improve in these clonal crops because it is recessive and linked to undesirable agronomic traits. In blackberry and red raspberry, breeding programs have used recessive mutants at the S locus to generate prickleless cultivars for the last century. In this study, we identified independent loss-of-function mutations in a WUSCHEL-LIKE HOMEOBOX transcription factor, WOX1, as the genetic basis of the prickleless S locus in both blackberry and red raspberry. We mapped the S locus using integrated genome-wide association, bulked segregant analysis, and identity-by-descent analyses informed by breeding pedigrees. Additionally, we generated a genome sequence from Luther Burbanks prickleless blackberry variety Burbank Thornless that contained an additional allele of WOX1. To verify the genes role, we used gene editing to knock out WOX1 in an elite prickled commercial blackberry line. All edited plants were prickleless and lacked glandular trichomes, confirming that WOX1 controls a joint developmental pathway. Other plant traits were unchanged, indicating WOX1 is a specific and safe target for improvement. Gene editing can enable breeders to remove prickles directly from elite varieties, reducing the need for extensive breeding cycles and delivering safer, easier-to-harvest cultivars to growers.

plant biology↗

Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia

Accumulating evidence links pediatric cancers to prenatal transformation events, yet the influence of the developmental stage on oncogenesis remains elusive. We investigated how hematopoietic stem cell developmental stages affect leukemic transformation, disease progression, and therapy response using a novel, humanized model of NUP98::NSD1-driven pediatric acute myeloid leukemia, that is particularly aggressive with WT1 co-mutations. Fetal-derived hematopoietic stem cells readily transform into leukemia, and WT1 mutations further enhance stemness and alter lineage hierarchy. In contrast, stem cells from later developmental stages become progressively resistant to transformation. Single-cell analyses revealed that fetal-origin leukemia stem cells exhibit greater quiescence and reliance on oxidative phosphorylation than their postnatal counterparts. These differences drive distinct therapeutic responses, despite identical oncogenic mutations. In patients, onco-fetal transcriptional programs correlate with worse outcomes. By targeting key vulnerabilities of fetal-origin leukemia cells, we identified combination therapies that significantly reduce aggressiveness, highlighting the critical role of ontogeny in pediatric cancer treatment.

cancer biology↗