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Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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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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Genomics02:02

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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
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Single-cell genomics identifies cell type-specific molecular changes in autism.

Dmitry Velmeshev1,2, Lucas Schirmer3,4,5, Diane Jung3,2

  • 1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA. dmitry.velmeshev@ucsf.edu arnold.kriegstein@ucsf.edu.

Science (New York, N.Y.)
|May 18, 2019
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Summary
This summary is machine-generated.

Autism research reveals specific brain cell changes, particularly in excitatory neurons and microglia, impacting synaptic signaling and correlating with clinical severity. These findings link cortical circuit molecular alterations to autism behaviors.

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Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Autism exhibits clinical and genetic heterogeneity.
  • Previous bulk gene expression studies indicated convergent neocortical changes in autism.
  • Direct cell-type-specific analysis in autism brain tissue was previously limited.

Purpose of the Study:

  • To identify autism-associated transcriptomic changes in specific brain cell types.
  • To investigate the role of specific cell populations in the neurobiology of autism.

Main Methods:

  • Single-nucleus RNA sequencing (snRNA-seq) was performed on cortical tissue from individuals with autism.
  • Transcriptomic data was analyzed to pinpoint cell-type-specific gene expression alterations.

Main Results:

  • Synaptic signaling in upper-layer excitatory neurons and the molecular state of microglia were preferentially affected in autism.
  • Dysregulation of specific gene groups in cortico-cortical projection neurons correlated with autism clinical severity.
  • Identified cell-type-specific molecular signatures associated with autism.

Conclusions:

  • Molecular changes in upper-layer cortical circuits are implicated in autism.
  • Specific neuronal subtypes and microglia are key cellular players in autism pathophysiology.
  • Findings provide a cell-type resolution understanding of autism's molecular basis.