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
New Vitamin B12-Based Therapy Could Change How Brain Cancer Is Treated
Researchers have identified a vitamin B12–based compound that appears capable of crossing the blood–brain barrier and selectively accumulating in glioblastoma tissue. For decades, one of the biggest problems in brain cancer treatment has had [...]
Simple Fiber Supplement Cuts Knee Arthritis Pain in Just 6 Weeks, Study Finds
A daily inulin supplement may help reduce knee osteoarthritis pain while revealing a possible link between gut health, muscle function, and pain sensitivity. For millions of people living with knee osteoarthritis, managing chronic pain [...]
This Common Vitamin May Help Stop Prediabetes From Turning Into Diabetes
Vitamin D may help prevent type 2 diabetes in people with specific genetic variations, offering a possible path toward personalized diabetes prevention. More than 40% of U.S. adults have prediabetes, a condition in which [...]
Ebola, hantavirus: Is the world prepared for the next pandemic?
Funding cuts to health research and a growing antivaccine movement are making it harder than ever to respond to viruses. The World Health Organization (WHO) has declared that an Ebola outbreak in Uganda and [...]
May 2026 Healthcare News and Trends: Market Signals That Matter
Artificial intelligence is dominating headlines, telehealth has settled into a new normal, and digital health continues to promise transformation. However, much of what is being discussed in healthcare today reflects potential rather than reality. [...]
Scientists Rewire Donor Stem Cells To Outsmart Aggressive Blood Cancers
Researchers have tested a gene-edited stem cell transplant designed to shield healthy blood-forming cells from powerful cancer-targeting immunotherapies. For patients with highly aggressive blood cancers, stem cell transplantation can offer a rare chance at [...]
Recent Digital Health Trends, Insights and News – May 2026
Last month marked continued progress as digital health moves into its next phase — from AI expanding into drug discovery and core infrastructure to new federal pathways accelerating device access and home-based care. Together, [...]
Cancer Mystery Solved: Scientists Discover How Melanoma Becomes “Immortal”
Scientists have uncovered a previously overlooked mechanism that may help melanoma cells become effectively “immortal.” Cancer cells face a major problem before they can become deadly: They have to figure out how to stop [...]
How Visual Neurons Organize Thousands of Synaptic Inputs
Summary: A new study uncovered the organizational rules that determine how neurons in the primary visual cortex process information. By imaging both the cell bodies (soma) and the individual synapses (on dendritic spines) of [...]
Scientists Just Found a Surprising Way To Destroy “Forever Chemicals”
Scientists have uncovered a new mechanism that may help break down highly persistent PFAS pollutants. PFAS have earned the nickname “forever chemicals” for a reason. These industrial compounds are so chemically durable that they [...]
Scientists Discover Cheap Material That Kills Deadly Superbugs
A new sulfur-rich antimicrobial polymer shows strong effectiveness against fungal and bacterial pathogens and may offer an affordable solution to antimicrobial resistance. Antimicrobial resistance is creating growing challenges for both healthcare and food production, [...]
What to Know About Cicada, or BA.3.2, the Latest SARS-CoV-2 Variant Under Monitoring
Like periodical cicadas, the insects for which it is nicknamed, SARS-CoV-2 Omicron subvariant BA.3.2 is only just beginning to emerge after lying low for an extended period since it first appeared. Although it was [...]
Scientists Say This Simple Supplement May Actually Reverse Heart Disease
Scientists in Japan say a common supplement may actually help “unclog” certain diseased heart arteries from the inside out. A simple food supplement sold in Japan may have helped reverse a dangerous form of [...]
New breakthrough against radiation: Korean Scientists create revolutionary shield with nanotechnology
Korean Scientists develop new nanotechnology material capable of reducing radiation impacts in space missions, hospitals, and power plants. The search for more efficient protection technologies in extreme environments has just gained an important advance. Korean [...]
Scientists Just Discovered the Hidden Trick That Keeps Your Cells Alive
A strange bead-like motion inside cells may be the secret to keeping their DNA—and health—in balance. Mitochondria are often described as the power plants of the cell because they produce the energy cells need [...]
Scientists Discover Stem Cells That Could Regrow Teeth and Bone
Scientists just uncovered the cellular “blueprint” that could one day let us regrow real teeth. Researchers at Science Tokyo have uncovered two distinct stem cell lineages that play a central role in forming tooth [...]
