Jon Patrick Connelly

Author Correction: cBAF complex components and MYC cooperate early in CD8+ T cell fate

Ao Guo, Hongling Huang, Zhexin Zhu, Jinan Chen et autres

us (code pays fourni par la source)

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

Alev Baysoy, Xiaolong Tian, Paul A. Renauer, Feifei Zhang et autres

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in …

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Essential HDRescue: A Co-Targeting Strategy to Enhance Precision Genome Editing by Co-Editing Essential Genes

Jamaica F. Siwak, Jon Patrick Connelly, Shondra M. Pruett‐Miller

Genome editing is widely used and conceptually simple, yet in practice, it is hindered by laborious workflows and high costs. These challenges stem from the difficulty of identifying and isolating cells that contain the desired user-defined modifications, a problem compounded by the …

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Dominant clones leverage developmental epigenomic states to drive ependymoma

Alisha Kardian, Hua Sun, Siri Manasa Ippagunta, Nicholas Laboe et autres

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain …

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Essential HDRescue: A Co‑Targeting Strategy to Enhance Precision Genome Editing by Co-Editing Essential Genes

J. Fay Siwak, Jon Patrick Connelly, Shondra M. Pruett‐Miller

Genome editing is widely used and conceptually simple, yet in practice, it is hindered by laborious workflows and high costs. These challenges stem from the difficulty of identifying and isolating cells that contain the desired user‑defined modifications, a problem compounded by the …

us (code pays fourni par la source)

Megabase-scale loss of heterozygosity provoked by CRISPR-Cas9 DNA double-strand breaks

Samantha B. Regan, Darpan Medhi, Yuanlin Xu, Travis White et autres

Harnessing DNA double-strand breaks (DSBs) is a powerful approach for gene editing, but it may provoke loss of heterozygosity (LOH), a common feature of tumor genomes. To interrogate this risk, we developed a flow cytometry-based system (Flo-LOH), detecting LOH in ∼5% of …

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EPCO-12. DOMINANT MALIGNANT LINEAGE LEVERAGE RESTRICTED EPIGENOMIC PROGRAMS TO DRIVE EPENDYMOMA DEVELOPMENT

Hua Sun, Alisha Kardian, Siri Manasa Ippagunta, Nicholas Laboe et autres

Abstract Pediatric cancers are often driven by unique alterations suggesting mechanistic ties to underlying developmental programs. Ependymoma (EPN) is an example of a brain cancer subtype driven by gene fusions involving ZFTA-RELA (ZR) that are exclusive to this disease. This leads to …

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RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity

Shivendra Vikram Singh, Jie Fang, Hongjian Jin, Lee-Ann Van de Velde et autres

The cellular plasticity of neuroblastoma is defined by a mixture of two major cell states, adrenergic and mesenchymal, which may contribute to therapy resistance. However, how neuroblastoma cells switch cellular states during therapy remains largely unknown, and how to eradicate neuroblastoma regardless …

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Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors

Rebecca R. J. Collins, Rebecca R. Florke Gee, Sima Tozandehjani, Tara Bayat et autres

Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB (G3 MB) subtype accounts for about 25% of MB and is associated with the worst outcomes. Herein, we report that more than half of G3 MB tumors express melanoma antigens …

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Spatially Resolved Panoramic in vivo CRISPR Screen via Perturb-DBiT

Rong Liang Fan, Alev Baysoy, Xiaolong Tian, Feifei Zhang et autres

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Author response: The context-dependent epigenetic and organogenesis programs determine 3D vs. 2D cellular fitness of MYC-driven murine liver cancer cells

Jie Fang, Shivendra Vikram Singh, Brennan Wells, Qiong Wu et autres

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The context-dependent epigenetic and organogenesis programs determine 3D vs. 2D cellular fitness of MYC-driven murine liver cancer cells

Jie Fang, Shivendra Vikram Singh, Brennan Wells, Qiong Wu et autres

3D cellular-specific epigenetic and transcriptomic reprogramming is critical to organogenesis and tumorigenesis. Here, we dissect the distinct cell fitness in 2D (normoxia vs. chronic hypoxia) vs 3D (normoxia) culture conditions for an MYC-driven murine liver cancer model. We identify over 600 shared …

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