Lin Tai

A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo

Sarah T. Diepstraten, Yexuan Deng, Margaret A. Potts, Amy Heidersbach et autres

CRISPR activation (CRISPRa) enables precise up-regulation of gene expression for ex vivo and in vivo applications. However, a lack of scalable, high-coverage tools has limited comprehensive genetic screening in murine models. Here, we introduce Partita, a next-generation mouse whole-genome CRISPRa sgRNA platform, …

au, cn (code pays fourni par la source)

3107 – ADVANCED CRISPR KNOCKOUT AND ACTIVATION MOUSE MODELS AS TOOLS FOR INVESTIGATING HEMATOLOGY AND HEMATOLOGICAL MALIGNANCIES

John E. La Marca, Sarah T. Diepstraten, Wei Jin, Yexuan Deng et autres

au (code pays fourni par la source)

Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma

Margaret A. Potts, Shinsuke Mizutani, Yexuan Deng, Srimayee Vaidyanathan et autres

Identifying tumor suppressor genes is predicted to inform on the development of novel strategies for cancer therapy. To identify new lymphoma driving processes that cooperate with oncogenic MYC, which is abnormally highly expressed in ~70% of human cancers, we use a genome-wide …

au, jp, cn, sg, us (code pays fourni par la source)

A novel, high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo

Sarah T. Diepstraten, Yexuan Deng, Margaret A. Potts, Amy J. Heidersbach et autres

Abstract CRISPR activation (CRISPRa) enables precise, locus-specific upregulation of gene expression, offering potential for both ex vivo and in vivo applications. However, the lack of scalable, high-coverage tools has limited its use in comprehensive genetic screens, particularly in murine models. Here, we …

au, cn, ca (code pays fourni par la source)

Transcriptomic changes including p53 dysregulation prime DNMT3A mutant cells for transformation

Erin Lawrence, Amali Cooray, Andrew J. Kueh, Martin Pál et autres

Abstract DNMT3A mutations are prevalent in haematologic malignancies. In our mouse model the murine homologue (R878H) of the human ‘hotspot’ R882H mutation is introduced into the mouse Dnmt3a locus. This results in globally reduced DNA methylation in all tissues. Mice with heterozygous …

au, gb (code pays fourni par la source)

Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening

Wei Jin, Yexuan Deng, John E. La Marca, Emily J. Lelliott et autres

Cas12a is a next-generation gene editing tool that enables multiplexed gene targeting. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a (enAsCas12a) linked to an mCherry fluorescent reporter. We demonstrate efficient single and multiplexed gene editing in vitro, …

au, cn, ca (code pays fourni par la source)

Mouse models to investigate in situ cell fate decisions induced by p53

Elizabeth Lieschke, Annabella Thomas, Andrew J. Kueh, Georgia K. Atkin‐Smith et autres

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 …

au, gb, ie (code pays fourni par la source)

Transcriptomic alterations including p53 pathway dysregulation prime DNMT3A mutant cells for transformation

Erin Lawrence, Amali Cooray, Andrew J. Kueh, Martin Pál et autres

DNMT3A mutations are prevalent in haematologic malignancies. Our mouse model introduced the murine homologue (R878H) of the human hotspot R882H mutation into the mouse Dnmt3a locus, resulting in globally reduced DNA methylation in all tissues. Mice with heterozygous R878H mutations developed gamma-radiation …

au (code pays fourni par la source)

Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening

Wei Jin, Yexuan Deng, John E. La Marca, Emily J. Lelliott et autres

Abstract Cas12a is a gene-editing tool that simplifies multiplexed gene targeting through its RNase activity, enabling maturation of individual crRNAs from a pre-crRNA-encoding RNA. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a ( enAsCas12a ) linked to …

au, cn (code pays fourni par la source)

Supplementary Data Figure S24 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells

Zilu Wang, Matteo Burigotto, Sabrina Ghetti, François Vaillant et autres

Supplementary Figure S24 showing that removal of mutant TP53 does not impair the in vitro growth of human colon cancer derived organoids

Supplementary Data Figure S3 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells

Zilu Wang, Matteo Burigotto, Sabrina Ghetti, François Vaillant et autres

Supplementary Figure S3 showing that removal of mutant TP53 does not impair the ability of diverse human cancer cell lines to adapt to conditions of stress

Data from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells

Zilu Wang, Matteo Burigotto, Sabrina Ghetti, François Vaillant et autres

Abstract Mutations in the tumor suppressor TP53 cause cancer and impart poor chemotherapeutic responses, reportedly through loss-of-function, dominant-negative effects and gain-of-function (GOF) activities. The relative contributions of these attributes is unknown. We found that removal of 12 different TP53 mutants with reported …