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Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors.

Sydney M Shaffer1, Benjamin L Emert2, Raúl A Reyes Hueros3

  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.

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Cellular gene expression fluctuations can last beyond cell division, revealing a form of biological memory. This study introduces MemorySeq to identify genes with persistent, non-genetic expression changes across generations.

Keywords:
cancer drug resistancegene expression memorysingle-cell

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Area of Science:

  • Cellular biology
  • Genomics
  • Epigenetics

Background:

  • Individual cells exhibit significant gene expression variability due to non-genetic factors.
  • The duration of these gene expression fluctuations, particularly beyond a single cell division, is not well understood.
  • Existing single-cell gene expression measurement techniques are limited to single time points, hindering the study of cellular memory.

Purpose of the Study:

  • To investigate whether non-genetic gene expression fluctuations in single cells can persist for multiple cell divisions.
  • To develop and apply a novel method for identifying genes with long-lasting, non-genetic expression changes.
  • To explore the biological implications of such persistent cellular memory.

Main Methods:

  • Combined Luria and Delbrück's fluctuation analysis with population-based RNA sequencing.
  • Developed and utilized a method termed MemorySeq to identify transcriptome-wide gene fluctuations persisting over several cell divisions.
  • Analyzed rare cell subpopulations within homogeneous clonal populations.

Main Results:

  • Identified multiple gene modules exhibiting coordinated expression in rare cells within clonal populations.
  • These rare subpopulations displayed distinct biological behaviors, including proliferation during anti-cancer therapy.
  • Demonstrated that non-genetic, multigenerational gene expression fluctuations can be quantitatively measured.

Conclusions:

  • Non-genetic factors can induce heritable cellular states that persist across multiple cell divisions, representing a form of biological memory.
  • The MemorySeq method enables the identification and characterization of genes involved in non-genetic cellular memory.
  • This finding suggests that non-genetic heritability of cellular state is a quantifiable biological property with potential implications for disease and therapy.