Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants.

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Cytometric Profiling of CD133+ Cells in Human Colon Carcinoma Cell Lines Identifies a Common core Phenotype and Cell Type-specific Mosaics

The International Journal of Biological Markers ◽

10.5301/jbm.5000020 ◽

2013 ◽

Vol 28 (3) ◽

pp. 267-273 ◽

Cited By ~ 11

Author(s):

Marica Gemei ◽

Rosa Di Noto ◽

Peppino Mirabelli ◽

Luigi Del Vecchio

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Colon Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Cell Type ◽

Carcinoma Cell Lines ◽

Cell Type Specific

In colorectal cancer, CD133+ cells from fresh biopsies proved to be more tumorigenic than their CD133– counterparts. Nevertheless, the function of CD133 protein in tumorigenic cells seems only marginal. Moreover, CD133 expression alone is insufficient to isolate true cancer stem cells, since only 1 out of 262 CD133+ cells actually displays stem-cell capacity. Thus, new markers for colorectal cancer stem cells are needed. Here, we show the extensive characterization of CD133+ cells in 5 different colon carcinoma continuous cell lines (HT29, HCT116, Caco2, GEO and LS174T), each representing a different maturation level of colorectal cancer cells. Markers associated with stemness, tumorigenesis and metastatic potential were selected. We identified 6 molecules consistently present on CD133+ cells: CD9, CD29, CD49b, CD59, CD151, and CD326. By contrast, CD24, CD26, CD54, CD66c, CD81, CD90, CD99, CD112, CD164, CD166, and CD200 showed a discontinuous behavior, which led us to identify cell type-specific surface antigen mosaics. Finally, some antigens, e.g. CD227, indicated the possibility of classifying the CD133+ cells into 2 subsets likely exhibiting specific features. This study reports, for the first time, an extended characterization of the CD133+ cells in colon carcinoma cell lines and provides a “dictionary” of antigens to be used in colorectal cancer research.

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Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines

Molecular Biology Reports ◽

10.1007/s11033-021-06786-z ◽

2021 ◽

Author(s):

Ezgi Avsar Abdik ◽

Hüseyin Abdik ◽

Duygu Turan ◽

Fikrettin Sahin ◽

Martin R. Berger ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Castration Resistant Prostate Cancer ◽

Cell Type ◽

Prostate Cancer Cell Lines ◽

Castration Resistant ◽

Cell Type Specific

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Cell type-specific Expression of JC Virus T Antigen in Primary and Established Cell Lines from Transgenic Mice

Journal of General Virology ◽

10.1099/0022-1317-71-1-151 ◽

1990 ◽

Vol 71 (1) ◽

pp. 151-164 ◽

Cited By ~ 9

Author(s):

A. H. Beggs ◽

J. H. Miner ◽

G. A. Scangos

Keyword(s):

Transgenic Mice ◽

Cell Lines ◽

Jc Virus ◽

T Antigen ◽

Cell Type ◽

Specific Expression ◽

Established Cell Lines ◽

Cell Type Specific Expression ◽

Established Cell ◽

Cell Type Specific

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Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

International Journal of Molecular Sciences ◽

10.3390/ijms21051661 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1661

Author(s):

Anamarija Mojzeš ◽

Marko Tomljanović ◽

Lidija Milković ◽

Renata Novak Kujundžić ◽

Ana Čipak Gašparović ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Warburg Effect ◽

Aerobic Glycolysis ◽

Intracellular Localization ◽

Lactate Production ◽

Glucose Consumption ◽

Cell Type ◽

Cell Type Specific ◽

The Warburg Effect

In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant.

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Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines

Lung Cancer ◽

10.1016/0169-5002(90)90124-5 ◽

1990 ◽

Vol 6 (3-4) ◽

pp. 120

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Growth Kinetics ◽

Human Lung ◽

Human Lung Cancer ◽

Cell Type ◽

Lung Cancer Cell ◽

Specific Receptor ◽

Cell Type Specific

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Cell Type-Specific TGF-β Mediated EMT in 3D and 2D Models and Its Reversal by TGF-β Receptor Kinase Inhibitor in Ovarian Cancer Cell Lines

International Journal of Molecular Sciences ◽

10.3390/ijms20143568 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3568 ◽

Cited By ~ 4

Author(s):

Wafa Al Ameri ◽

Ikhlak Ahmed ◽

Fatima M. Al-Dasim ◽

Yasmin Ali Mohamoud ◽

Iman K. Al-Azwani ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

3D Models ◽

Cancer Cell Lines ◽

Cell Type ◽

Ovarian Cancer Cell Lines ◽

Cell Type Specific ◽

Β Receptor

Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-β-mediated and cell adhesion pathways. Presence of TGF-β in these cell lines shows an increased invasion potential which is specific to cell type. In the present study, we identified exogenous addition of TGF-β can induce Epithelial to Mesenchymal Transition (EMT) in a few cancer cell lines. RNA sequencing and real time PCR were carried out in different ovarian cancer cell lines to identify molecular profiling and metabolic profiling. Since EMT induction by TGF-β is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-β modulation in EMT and cancer invasion were successfully depicted in both 2D and 3D models of SKOV3 and CAOV3 cell lines. Functional evaluation in 3D and 2D models demonstrates that the addition of the exogenous TGF-β can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-β receptor kinase I inhibitor (LY364947) can revert the TGF-β effect in these cells. In a nutshell, TGF-β can induce EMT and migration, increase aggressiveness, increase cell survival, alter cell characteristics, remodel the Extracellular Matrix (ECM) and increase cell metabolism favorable for tumor invasion and metastasis. We concluded that transcriptomic and phenotypic effect of TGF-β and its inhibitor is cell-type specific and not cancer specific.

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Independent glial subtypes delay development and extend healthy lifespan upon reduced insulin-PI3K signalling

BMC Biology ◽

10.1186/s12915-020-00854-9 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Nathaniel S. Woodling ◽

Arjunan Rajasingam ◽

Lucy J. Minkley ◽

Alberto Rizzo ◽

Linda Partridge

Keyword(s):

Glial Cell ◽

Cell Types ◽

Therapeutic Interventions ◽

Developmental Timing ◽

Cell Type ◽

Specific Effects ◽

Trade Offs ◽

Distinct Cell ◽

Pi3k Signalling ◽

Cell Type Specific

Abstract Background The increasing age of global populations highlights the urgent need to understand the biological underpinnings of ageing. To this end, inhibition of the insulin/insulin-like signalling (IIS) pathway can extend healthy lifespan in diverse animal species, but with trade-offs including delayed development. It is possible that distinct cell types underlie effects on development and ageing; cell-type-specific strategies could therefore potentially avoid negative trade-offs when targeting diseases of ageing, including prevalent neurodegenerative diseases. The highly conserved diversity of neuronal and non-neuronal (glial) cell types in the Drosophila nervous system makes it an attractive system to address this possibility. We have thus investigated whether IIS in distinct glial cell populations differentially modulates development and lifespan in Drosophila. Results We report here that glia-specific IIS inhibition, using several genetic means, delays development while extending healthy lifespan. The effects on lifespan can be recapitulated by adult-onset IIS inhibition, whereas developmental IIS inhibition is dispensable for modulation of lifespan. Notably, the effects we observe on both lifespan and development act through the PI3K branch of the IIS pathway and are dependent on the transcription factor FOXO. Finally, IIS inhibition in several glial subtypes can delay development without extending lifespan, whereas the same manipulations in astrocyte-like glia alone are sufficient to extend lifespan without altering developmental timing. Conclusions These findings reveal a role for distinct glial subpopulations in the organism-wide modulation of development and lifespan, with IIS in astrocyte-like glia contributing to lifespan modulation but not to developmental timing. Our results enable a more complete picture of the cell-type-specific effects of the IIS network, a pathway whose evolutionary conservation in humans make it tractable for therapeutic interventions. Our findings therefore underscore the necessity for cell-type-specific strategies to optimise interventions for the diseases of ageing.

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