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Related Concept Videos

Life Histories01:29

Life Histories

Constrained by limited energy and resources, organisms must compromise between offspring quantity and parental investment. This trade-off is represented by two primary reproductive strategies; K-strategists produce few offspring but provide substantial parental support, whereas r-strategists produce much progeny that receives little care. These strategies are related to an organism’s survival likelihood across its lifespan, which is represented by a survivorship curve. Three general types of...
Energy Budgets and Reproductive Strategies00:51

Energy Budgets and Reproductive Strategies

Organisms must balance energy intake with the energy required for growth, maintenance, and reproduction. These trade-offs result in a variety of survivorship and reproductive strategies, including semelparity and iteroparity. Semelparous species reproduce only once in their lifetime, often investing most available resources into that single reproductive event. Iteroparous species, by contrast, reproduce multiple times over their lifetimes, typically allocating fewer resources to any single...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
Endospores and Sporulation01:20

Endospores and Sporulation

Endospores are specialized, dormant cells primarily formed by Gram-positive bacteria, including Bacillus and Clostridium, enabling survival under extreme environmental conditions. Due to their unique composition and formation process, these structures are highly resistant to physical and chemical insults, such as extreme heat, ultraviolet and ionizing radiation, desiccation, and toxic chemicals. Rare instances of endospore-like structures have also been observed in some Gram-negative bacteria,...

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Techniques to Induce and Quantify Cellular Senescence
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Persistence and/or Senescence: Not So Lasting at Last?

Clemens A Schmitt1,2,3,4

  • 1Medical Department of Hematology, Oncology and Tumor Immunology, Molekulares Krebsforschungszentrum - MKFZ, Campus Virchow Klinikum, Charité - Universitätsmedizin, Berlin, Germany.

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Drug-tolerant cancer persister cells exhibit a unique arrest state, distinct from typical senescence. Targeting one-carbon metabolism and H4K20 methylation reveals vulnerabilities in these aggressive relapse-driving cells.

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Area of Science:

  • Cancer Biology
  • Epigenetics
  • Cellular Senescence

Background:

  • Therapy-resistant cancer cells can persist, leading to aggressive relapses.
  • These drug-tolerant persisters are often characterized as senescent or senescence-like.
  • Understanding persister cell biology is crucial for overcoming treatment failure.

Purpose of the Study:

  • To model drug-tolerant persistence using embryonic diapause-like arrest (DLA) in cancer cells.
  • To compare DLA-induced persistence with therapy-induced senescence.
  • To identify epigenetic vulnerabilities of DLA-like persister cells.

Main Methods:

  • Utilized mTOR/PI3K inhibitor to induce DLA in lung cancer and melanoma cells.
  • Compared DLA phenotype with therapy-induced senescence.
  • Performed CRISPR dropout screens to identify genetic dependencies.
  • Investigated the role of one-carbon metabolism and H4K20 methylation.

Main Results:

  • DLA cells showed some, but not all, features of senescence, notably lacking the inflammatory senescence-associated secretory phenotype (SASP).
  • CRISPR screens identified one-carbon metabolism and H4K20me3 as critical for DLA-like persisters.
  • H4K20me3 selectively repressed SASP-related IFN response genes in DLA cells.
  • Inhibition of KMT5B/C methyltransferases was toxic to DLA cells by derepressing inflammatory programs.

Conclusions:

  • DLA serves as a distinct model for studying drug-tolerant cancer persistence.
  • Epigenetic regulation, specifically H4K20 methylation, plays a key role in DLA-like persister cell characteristics.
  • Targeting one-carbon metabolism and H4K20-active methyltransferases presents potential therapeutic strategies against persister cells.
  • The study highlights challenges in modeling persister cells using cultured cell lines.