Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition.
A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC Laboratory of Medical Sciences has revealed that the contribution of cells expressing maternal or paternal X chromosomes can be selectively skewed in different parts of the body. The study leverages human data from the 1000 Genomes Project combined with mouse models of human X chromosome-linked DNA sequence variation to advance our fundamental understanding of development in biologically female individuals who have two X chromosomes.
Mechanisms Behind X Chromosome Selection
Until now, it was thought that the usage of maternal and paternal X-chromosomes was similar throughout the body. The new work shows that this is not always true, and that different organs may be skewed towards using either maternal or paternal X-chromosomes. The work also reveals the process driving this skew: competition between cells expressing either one or the other X-chromosome. In some individuals, cells in organs such as the heart mostly use the X chromosome from one parent, whereas immune cells almost exclusively utilize the X chromosome from the other parent. This provides an important step forward in understanding the underlying principles and mechanisms of development in XX individuals.
Implications of X Chromosome Selection
Biological females inherit two X chromosomes – one from each parent – along with all the other genetic material that builds and sustains the body. But despite the presence of both parental X chromosomes, only one X chromosome is actively expressed in any given cell. Since the DNA sequence of each X chromosome has genetic variations, each cell effectively chooses to express a set of unique characteristics derived from either one or the other parent.
“We realized that when cells chose one of their two X chromosomes over the other, they also chose which set of genetic variants to express,” said Matthias Merkenschlager, who leads the Lymphocyte Development Research Group. “As a result, individual cells express distinct genetic variants. We are now working to find out more about how X-linked genetic variants shape organismal development, and whether selective X chromosome usage in specific tissues may affect the likelihood of certain conditions later in life.”
Research Focus on the STAG2 Gene
The researchers focussed on a specific gene on the X chromosome, called STAG2. They found that cells with a genetic variant of STAG2 failed to develop into immune cells called lymphocytes in females that carried variant STAG2 on one X chromosome, and the common (‘reference’) version of STAG2 on the other X chromosome.
By contrast, cells with the same variant of STAG2 were fully competent to form lymphocytes in XY males (with a single copy of the X chromosome), or females in which both X chromosomes carried the variant.
The researchers concluded that what prevents variant cells from forming lymphocytes is not the variant as such, but the presence of cells expressing the reference version of STAG2. This shows that cells compete for ‘permission’ to form specific cell types within the body. The findings reveal a new aspect of X-linked diversity not previously appreciated: that interactions between cells can shape the contribution of X-linked diversity to specific cell types and tissues.
Even if cells expressing reference STAG2 outcompete to form the blood, cells expressing the variant may predominate in other parts of the body. For the study’s lead author Teresa Buenaventura, this sparked a personal curiosity: “’Working on this project has been particularly exciting for me since it has made me curious about the contribution of each of the X chromosomes to my different tissues,” she said.
These findings reveal a previously underappreciated aspect of X-linked diversity, where interactions between epigenetically diverse clones can shape the contribution of X-linked genetic diversity to specific cell types and tissues.
Reference: “Competition shapes the landscape of X-chromosome-linked genetic diversity” 25 July 2024, Nature Genetics.
DOI: 10.1038/s41588-024-01840-5
News
Does Space-Time Really Exist?
Is time something that flows — or just an illusion? Exploring space-time as either a fixed “block universe” or a dynamic fabric reveals deeper mysteries about existence, change, and the very nature of reality. [...]
Unlocking hidden soil microbes for new antibiotics
Most bacteria cannot be cultured in the lab-and that's been bad news for medicine. Many of our frontline antibiotics originated from microbes, yet as antibiotic resistance spreads and drug pipelines run dry, the soil [...]
By working together, cells can extend their senses beyond their direct environment
The story of the princess and the pea evokes an image of a highly sensitive young royal woman so refined, she can sense a pea under a stack of mattresses. When it comes to [...]
Overworked Brain Cells May Hold the Key to Parkinson’s
Scientists at Gladstone Institutes uncovered a surprising reason why dopamine-producing neurons, crucial for smooth body movements, die in Parkinson’s disease. In mice, when these neurons were kept overactive for weeks, they began to falter, [...]
Old tires find new life: Rubber particles strengthen superhydrophobic coatings against corrosion
Development of highly robust superhydrophobic anti-corrosion coating using recycled tire rubber particles. Superhydrophobic materials offer a strategy for developing marine anti-corrosion materials due to their low solid-liquid contact area and low surface energy. However, [...]
This implant could soon allow you to read minds
Mind reading: Long a science fiction fantasy, today an increasingly concrete scientific goal. Researchers at Stanford University have succeeded in decoding internal language in real time thanks to a brain implant and artificial intelligence. [...]
A New Weapon Against Cancer: Cold Plasma Destroys Hidden Tumor Cells
Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers. Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and [...]
This Common Sleep Aid May Also Protect Your Brain From Alzheimer’s
Lemborexant and similar sleep medications show potential for treating tau-related disorders, including Alzheimer’s disease. New research from Washington University School of Medicine in St. Louis shows that a commonly used sleep medication can restore normal sleep patterns and [...]
Sugar-Coated Nanoparticles Boost Cancer Drug Efficacy
A team of researchers at the University of Mississippi has discovered that coating cancer treatment carrying nanoparticles in a sugar-like material increases their treatment efficacy. They reported their findings in Advanced Healthcare Materials. Over a tenth of breast [...]
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
