Telomerase-Independent Proliferation Is Influenced by Cell Type in Saccharomyces cerevisiae

Abstract Yeast strains harboring mutations in genes required for telomerase function (TLC1 and the EST genes) exhibit progressive shortening of telomeric DNA and replicative senescence. A minority of cells withstands loss of telomerase through RAD52-dependent amplification of telomeric and subtelomeric sequences; such survivors are now capable of long-term propagation with telomeres maintained by recombination rather than by telomerase. Here we report that simultaneous expression in haploid cells of both MATa and MATα information suppresses the senescence of telomerase-deficient mutants, with suppression occurring via the RAD52-dependent survivor pathway(s). Such suppression can be mimicked by deletion of SIR1-SIR4, genes that function in transcriptional silencing of several loci including the silent mating-type loci. Furthermore, telomerase-defective diploid strains that express only MATa or MATα information senesce at a faster rate than telomerase-defective diploids that are heterozygous at the MAT locus. This suggests that the RAD52-dependent pathway(s) for telomere maintenance respond to changes in the levels of recombination, a process regulated in part by the hierarchy of gene control that includes MAT regulation. We propose that cell-type-specific regulation of recombination at human telomeres may similarly contribute to the tissue-specific patterns of disease found in telomerase-deficient tumors.

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Cell type-specific regulation of amniotic fibronectin expression by Glucocorticoid (GC): Conservation of GC responsiveness in humans and non-human primates

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86698-1 ◽

1998 ◽

Vol 5 (1) ◽

pp. 191A-191A

Author(s):

Y MA ◽

A BUNIM ◽

D GIUSSANI ◽

P NATHANIELSZ ◽

C LOCKWOOD ◽

...

Keyword(s):

Cell Type ◽

Fibronectin Expression ◽

Cell Type Specific ◽

Specific Regulation

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Faculty Opinions recommendation of Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1119471.580547 ◽

2008 ◽

Author(s):

Guoping Feng ◽

Jonathan Ting

Keyword(s):

Antipsychotic Drugs ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation

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Osteogenic differentiation of human mesenchymal stromal cells and fibroblasts differs depending on tissue origin and replicative senescence

Scientific Reports ◽

10.1038/s41598-021-91501-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vera Grotheer ◽

Nadine Skrynecki ◽

Lisa Oezel ◽

Jan Grassmann ◽

Joachim Windolf ◽

...

Keyword(s):

Cell Culture ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Replicative Senescence ◽

Cell Type ◽

Differentiation Potential ◽

Culture Passage ◽

Cell Type Specific ◽

Cell Culture Passage ◽

Tissue Origin

AbstractThe need for an autologous cell source for bone tissue engineering and medical applications has led researchers to explore multipotent mesenchymal stromal cells (MSC), which show stem cell plasticity, in various human tissues. However, MSC with different tissue origins vary in their biological properties and their capability for osteogenic differentiation. Furthermore, MSC-based therapies require large-scale ex vivo expansion, accompanied by cell type-specific replicative senescence, which affects osteogenic differentiation. To elucidate cell type-specific differences in the osteogenic differentiation potential and replicative senescence, we analysed the impact of BMP and TGF-β signaling in adipose-derived stromal cells (ASC), fibroblasts (FB), and dental pulp stromal cells (DSC). We used inhibitors of BMP and TGF-β signaling, such as SB431542, dorsomorphin and/or a supplemental addition of BMP-2. The expression of high-affinity binding receptors for BMP-2 and calcium deposition with alizarin red S were evaluated to assess osteogenic differentiation potential. Our study demonstrated that TGF-β signaling inhibits osteogenic differentiation of ASC, DSC and FB in the early cell culture passages. Moreover, DSC had the best osteogenic differentiation potential and an activation of BMP signaling with BMP-2 could further enhance this capacity. This phenomenon is likely due to an increased expression of activin receptor-like kinase-3 and -6. However, in DSC with replicative senescence (in cell culture passage 10), osteogenic differentiation sharply decreased, and the simultaneous use of BMP-2 and SB431542 did not result in further improvement of this process. In comparison, ASC retain a similar osteogenic differentiation potential regardless of whether they were in the early (cell culture passage 3) or later (cell culture passage 10) stages. Our study elucidated that ASC, DSC, and FB vary functionally in their osteogenic differentiation, depending on their tissue origin and replicative senescence. Therefore, our study provides important insights for cell-based therapies to optimize prospective bone tissue engineering strategies.

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Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

Molecular Psychiatry ◽

10.1038/s41380-021-01217-8 ◽

2021 ◽

Author(s):

Hee-Dae Kim ◽

Jing Wei ◽

Tanessa Call ◽

Nicole Teru Quintus ◽

Alexander J. Summers ◽

...

Keyword(s):

Nucleus Accumbens ◽

Molecular Mechanisms ◽

Cell Types ◽

Current Treatment ◽

Specific Cell ◽

Excitatory Synapses ◽

Cell Type ◽

Cell Type Specific ◽

Specific Regulation ◽

Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

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