Genome-wide CRISPR screen identifies noncanonical NF-κB signaling as a regulator of density-dependent proliferation

Fomicheva, Maria; Macara, Ian G.

doi:10.7554/elife.63603

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…The NF‐κB family comprises five TFs, including p65/RELA, RELB, c‐REL, p50 (its progenitor p105), and p52 (its precursor p100), 134 which play essential roles in inflammation, 135 immunology, 136 cell proliferation, 137 and differentiation 138 . The mature proteins p65/RELA, RELB, and c‐REL possess a C‐terminal TAD within their respective C‐terminal portions 139 .…”

Section: Redox Signaling Network In Cellular Homeostasismentioning

confidence: 99%

Redox signaling at the crossroads of human health and disease

Zuo

Zhang

Luo

et al. 2022

MedComm

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Redox biology is at the core of life sciences, accompanied by the close correlation of redox processes with biological activities. Redox homeostasis is a prerequisite for human health, in which the physiological levels of nonradical reactive oxygen species (ROS) function as the primary second messengers to modulate physiological redox signaling by orchestrating multiple redox sensors. However, excessive ROS accumulation, termed oxidative stress (OS), leads to biomolecule damage and subsequent occurrence of various diseases such as type 2 diabetes, atherosclerosis, and cancer. Herein, starting with the evolution of redox biology, we reveal the roles of ROS as multifaceted physiological modulators to mediate redox signaling and sustain redox homeostasis. In addition, we also emphasize the detailed OS mechanisms involved in the initiation and development of several important diseases. ROS as a double‐edged sword in disease progression suggest two different therapeutic strategies to treat redox‐relevant diseases, in which targeting ROS sources and redox‐related effectors to manipulate redox homeostasis will largely promote precision medicine. Therefore, a comprehensive understanding of the redox signaling networks under physiological and pathological conditions will facilitate the development of redox medicine and benefit patients with redox‐relevant diseases.

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Section: Redox Signaling Network In Cellular Homeostasismentioning

confidence: 99%

Redox signaling at the crossroads of human health and disease

Zuo

Zhang

Luo

et al. 2022

MedComm

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“…The DDX20 Dependence and the EGFR Gene Effect at Hepatocellular Carcinoma (HCC) Cell Lines. Tumor cellessential genes can be screened through CRISPR-based [18] and shRNA-based [19] genome editing. To investigate DDX20 essentiality in HCC cells, we leveraged CGPE, which can generate genetic dependencies of mRNA in tumor cells by pooled RNAi or CRISPR screening data.…”

Section: Ddx20 Expression Is Associated With Immune-mentioning

confidence: 99%

A Macrophage Differentiation-Mediated Gene: DDX20 as a Molecular Biomarker Encompassing the Tumor Microenvironment, Disease Staging, and Prognoses in Hepatocellular Carcinoma

Yang

Pang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. DDX20 involves the mechanism of cell proliferate, mitogenic Ets transcriptional suppressor (METS), which can arrest the cell cycle of macrophages. However, little is known about DDX20 expression, clinical values, and the relationship with tumor microenvironment in HCC. Methods. We mined the transcriptional, protein expression and survival data of DDX20 in HCC from online databases. The immunological effects of DDX20 were estimated by bioinformatic algorithms. The RNAi and CRISPR screening were used to assess the gene effect of DDX20 for the EGFR gene in liver tumor cell. Results. We found that the DDX20 was highly expressed in HCC. The qRT-PCR result shows a significantly upregulated DDX20 expression in HCC samples from the West China Hospital. The high mRNA expression of DDX20 is associated with a poor survival. DDX20 expression is positively correlated with MDSCs in HCC tissues. Moreover, DDX20 has a high predicted ability for the response to immunotherapy. Furthermore, hsa-mir-324-5p could regulate the macrophage differentiation by interacting with DDX20. Meanwhile, the EGFR gene gets a high dependency score for DDX20. Conclusion. In sum, DDX20 may serve as a prognostic marker for worse clinical outcomes with HCC and potentially enable more precise and personalized immunotherapeutic strategies in the future.

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“…gTGFbR1 Fw 5'-CACCGTTGACCTAATTCCTCGAGA -3'; gTGFbR1 Rv 5'-AAACGTCTCGAGGAATTAGGTCAAC -3'; gTGFbR2 Fw 5'-CACCGACCTGCAGGAG TACCTCACG -3'; gTGFbR2 Rv 5'-AAACCGTGAGGTACTCCTGCAGGTC -3'. The non-target gRNA sequence was as previously described (Fomicheva and Macara, 2020). gRNAs were inserted in the lentiCRISPR v2 plasmid (Addgene) (Sanjana et al, 2014).…”

Section: Primers and Grnasmentioning

confidence: 99%

“…gTGFbR1 Fw 5'-CACCGTTGACCTAATTCCTCGAGA -3'; gTGFbR1 Rv 5'-gRNA sequence was as previously described (Fomicheva and Macara, 2020). gRNAs were inserted in the lentiCRISPR v2 plasmid (Addgene) (Sanjana et al, 2014).…”

Section: Primers and Grnasmentioning

confidence: 99%

A Self-Limiting Circuit Regulates Mammary Cap Cell Plasticity Through TGF-beta Signaling

Guelte

Macara

2021

Preprint

Self Cite

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The organization and maintenance of complex tissues requires emergent properties driven by self-organizing and self-limiting cell-cell interactions. We examined these interactions in the murine mammary gland. Luminal and myoepithelial subpopulations of the postnatal mammary gland arise from unipotent progenitors, but the destiny of cap cells, which enclose terminal end buds (TEB) in pubertal mice, remains controversial. Using a transgenic strain (Tg11.5kb-GFP) that specifically marks cap cells, we found ~50% of these cells undergo divisions perpendicular to the TEB surface, suggesting they might contribute to the underlying luminal cell population. To address their stemness potential we developed a lineage tracing mouse driven from the s-SHIP (11.5 kb) promoter. Induction of tdTomato (tdTom) from this promoter in vivo demonstrated that all cap cell progeny are myoepithelial, with no conversion to luminal lineage. Organoid cultures also exhibited unipotency. However, isolated cap cells cultured as mammospheres generated mixed luminal/myoepithelial spheres. Moreover, ablation of luminal cells in vivo using diphtheria toxin triggered repopulation by progeny of tdTom+ cap cells. A signaling inhibitor screen identified the TGFb pathway as a potential regulator of multipotency. TGFbR inhibitors or gene deletion blocked conversion to the luminal lineage, consistent with an autocrine loop in which cap cells secrete TGFb to activate the receptor and promote luminal transdifferentiation. Ductal tree regeneration in vivo from isolated cap cells was much more efficient when they were pre-treated with inhibitor, consistent with more cells retaining cap cell potential prior to transplantation. Notably, in vitro transdifferentiation of cap cells was blocked by co-culture with luminal cells. Overall, these data reveal a self-limiting cell circuit through which mammary luminal cells suppress cap cell conversion to the luminal lineage.

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Genome-wide CRISPR screen identifies noncanonical NF-κB signaling as a regulator of density-dependent proliferation

Cited by 9 publications

References 44 publications

Redox signaling at the crossroads of human health and disease

Redox signaling at the crossroads of human health and disease

A Macrophage Differentiation-Mediated Gene: DDX20 as a Molecular Biomarker Encompassing the Tumor Microenvironment, Disease Staging, and Prognoses in Hepatocellular Carcinoma

A Self-Limiting Circuit Regulates Mammary Cap Cell Plasticity Through TGF-beta Signaling

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