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Related Concept Videos

Dosage Compensation02:50

Dosage Compensation

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In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with  distinct numbers of X chromosomes will...
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The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
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The Ratio of X Chromosome to Autosomes02:45

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In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.  
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X-linked Traits01:19

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In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
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X and Y Chromosomes02:32

X and Y Chromosomes

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Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Updated: Oct 7, 2025

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
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Genes That Escape X Chromosome Inactivation Modulate Sex Differences in Valve Myofibroblasts.

Brian A Aguado1,2,3,4, Cierra J Walker5,6, Joseph C Grim1,2

  • 1Department of Chemical and Biological Engineering (B.A.A., J.C.G., B.J.V., A.G.R., K.S.A.), University of Colorado, Boulder.

Circulation
|January 10, 2022
PubMed
Summary
This summary is machine-generated.

Sex differences in aortic valve stenosis involve distinct molecular pathways. Genes escaping X-chromosome inactivation contribute to higher myofibroblast activation in females, impacting disease progression.

Keywords:
aortic valve stenosisbiocompatible materialshydrogelssex characteristics

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Area of Science:

  • Cardiovascular Biology
  • Biomaterials Science
  • Genetics

Background:

  • Aortic valve stenosis exhibits sexual dimorphism, with distinct pathological features in women (fibrosis) and men (calcification).
  • The underlying intracellular molecular mechanisms driving these sex-specific differences are not well understood.

Purpose of the Study:

  • To investigate sex-specific molecular mechanisms of valvular interstitial cell (VIC) activation and deactivation.
  • To utilize a novel hydrogel biomaterial culture system to model the valve microenvironment and study sex-dependent VIC responses.

Main Methods:

  • Developed hydrogel biomaterials to culture sex-specific VICs and mimic the valve microenvironment.
  • Employed RNA sequencing to identify pathways involved in sex-dependent VIC activation.
  • Used small molecule inhibitors and siRNA to elucidate mechanisms of sex-specific cellular responses to microenvironmental cues.

Main Results:

  • Female VICs exhibited higher baseline α-smooth muscle actin (α-SMA) stress fibers than male VICs, with increased activation in response to matrix stiffness.
  • Transcriptomic analysis identified Rho-associated protein kinase (ROCK) signaling as a key driver of sex-dependent myofibroblast activation.
  • Genes escaping X-chromosome inactivation, such as BMX and STS, were found to partially regulate elevated female myofibroblast activation via ROCK signaling.

Conclusions:

  • Sex-dependent myofibroblast activation pathways are confirmed in vitro and in vivo.
  • Genes escaping X-chromosome inactivation play a role in sex differences in aortic valve stenosis progression.
  • Considering sex as a biological variable is crucial for understanding disease mechanisms and developing sex-based precision therapies.