(Press-News.org) Baltimore MD-- We would not expect a baby to join a team or participate in social situations that require sophisticated communication. Yet, most developmental biologists have assumed that young cells, only recently born from stem cells and known as "progenitors," are already competent at inter-communication with other cells.
New research from Carnegie's Allan Spradling and postdoctoral fellow Ming-Chia Lee shows that infant cells have to go through a developmental process that involves specific genes before they can take part in the group interactions that underlie normal cellular development and keep our tissues functioning smoothly. The existence of a childhood state where cells cannot communicate fully has potentially important implications for our understanding of how gene activity on chromosomes changes both during normal development and in cancerous cells. The work is published in Genes and Development.
The way that the molecules that package a cell's chromosomes are organized in order to control gene activity is known as the cell's "epigenetic state." The epigenetic state is fundamental to understanding Spradling and Lee's findings. To developmental biologists, changes in this epigenetic state ultimately explain how the cell's properties are altered during tissue maturation.
"In short, acquired epigenetic changes in a developing cell are reminiscent of the learned changes the brain undergoes during childhood," Spradling explained. "Just as it remains difficult to map exactly what happens in a child's brain as it learns, it is still very difficult to accurately measure epigenetic changes during cellular development. Not enough cells can usually be obtained that are at precisely the same stage for scientists to map specific molecules at specific chromosomal locations."
Lee and Spradling took advantage of the unsurpassed genetic tools available in the fruit fly to overcome these obstacles and provide new insight into the epigenetics of cellular development.
Using a variety of tools and techniques, they focused on cells in the fruit fly ovary and were able identify a specific gene called lsd1 that is needed for ovarian follicle progenitor cells to mature at their normal rate. The researchers found that the amount of the protein that is encoded by this gene, Lsd1, which is present in follicle progenitors decreases as the cells approach differentiation. What's more, the onset of differentiation could be shifted by changing the levels of Lsd1 protein that are present. They deduced that differentiation ensues when Lsd1 levels fall below a critical threshold, and that this likely corresponds to when genes can be stably expressed.
"The timing of differentiation is very important for normal development," Lee said. "Differentiation onset determines how many times progenitors divide, and even small perturbations in Lsd1 levels changed the number of follicle cells that were ultimately produced, which reduced ovarian function."
Previously, it was thought that the follicle cell progenitors started to differentiate based on an external signal they received from another kind of ovarian cells known as germ cells. Lee and Spradling found that while this germ cell signal was essential, it was already being regularly sent even before the progenitors responded. Instead, it was the Lsd1-mediated change in their epigenetic state that timed when progenitor cells started to respond to the signal and begun differentiating. Once they become competent, however, differentiating follicle cells communicate extensively with their neighbors, and continued to do so throughout their lives.
As is frequently the case in basic biological research, the molecules and mechanisms studied here are found in most multicellular animals and hence the researchers conclusions are likely to apply broadly throughout the animal kingdom, including in humans.
In addition, to the importance of this research for understanding how animal chromosomes change during normal development, it may also help clarify alterations in the epigenetic state that take place in some cancers. A minority of cells in such cancers begin to express high levels of Lsd1 and to behave like undifferentiated progenitors.
"Studying fruit fly follicle cell differentiation can teach us at a deeper level what Lsd1 is doing in both normal and cancerous progenitors," Lee added.
INFORMATION:
This work was funded in part by the Howard Hughes Medical Institute.
The Carnegie Institution for Science is a private, nonprofit organization headquartered in Washington, D.C., with six research departments throughout the U.S. Since its founding in 1902, the Carnegie Institution has been a pioneering force in basic scientific research. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.
TORONTO, ON - Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome - the controller - directs when a particular gene - the pilot - can perform its prescribed function.
A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the ...
White adipose tissue stores excess calories as fat that can be released for use in other organs during fasting. Mammals also have small amounts of brown adipose tissue, which primarily acts as an effective fat burner for the production of heat. Now researchers from the University of Southern Denmark have uncovered the mechanism by which white fat cells from humans gets reprogrammed to become browner.
Browning of white adipose tissue increases the energy consumption of the body and therefore constitutes a potential strategy for future treatment of obesity. The challenge ...
Immune cells perform a previously unsuspected role in the brain that may contribute to obesity, according to a new study by UC San Francisco researchers.
When the researchers fed mice a diet high in saturated milk fats, microglia, a type of immune cell, underwent a population explosion in the brain region called the hypothalamus, which is responsible for feeding behavior.
The researchers used an experimental drug and, alternatively, a genetic approach to knock out these microglia, and both strategies resulted in a complete loss of microglia-driven inflammation in the ...
PHOENIX, Ariz. -- Dec. 12, 2014 -- Using a basic genetic difference between men and women, the Translational Genomics Research Institute (TGen) has uncovered a way to track down the source of a neurological disorder in a young girl.
TGen's discovery relies on a simple genetic fact: Men have one X and one Y chromosome, while women have two X chromosomes. This women-only factor was leveraged by TGen investigators to develop a highly accurate method of tracking down a previously unrecognized disorder of the X-chromosome.
The study of a pre-teen girl, who went years ...
With the ball at the three-point line near the top of the key, what will Tim Duncan of the NBA's San Antonio Spurs do? Pass to a player posting up? Or does he take a shot? An analysis by Disney Research of player tracking data, however, suggests the highest probability is a pass to guard Tony Parker on his left.
It's just one play, by one player, in one sport - and perhaps not that hard for the average courtside observer to anticipate - but with the field of sports becoming more driven by sports analytics, predicting the next thing that a player will do has become a major ...
A new National Science Foundation (NSF) report reveals the number of U.S. citizen doctoral graduates in science, engineering and health fields, who remain in the United States, tracks closely with their intent to stay in the United States at the time of graduation. However, there are noticeable differences for doctoral graduates who were temporary visa holders at the time of graduation.
According to the report, 96.4 percent of U.S. citizen doctoral graduates from academic years 2001-09 reported their intent to live in the United States, a measure referred to as the expected ...
December 12, 2014 - All children should undergo vision health screening between age 36 and 72 months--preferably every year--using evidence-based test methods and with effective referral and follow-up, according to recommendations published in the January issue of Optometry and Vision Science, official journal of the American Academy of Optometry. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
The National Expert Panel to The National Center for Children's Vision Health makes recommendations for vision health screening in ...
MADISON, Wis. - As a fundamental unit of life, the cell is central to all of biology. Better understanding how complex cells evolved and work promises new revelations in areas as diverse as cancer research and developing new crop plants.
But deep thinking on how the eukaryotic cell came to be is astonishingly scant. Now, however, a bold new idea of how the eukaryotic cell and, by extension, all complex life came to be is giving scientists an opportunity to re-examine some of biology's key dogma.
All complex life -- including plants, animals and fungi -- is made up of ...
The genomes of modern birds tell a story: Today's winged rulers of the skies emerged and evolved after the mass extinction that wiped out dinosaurs and almost everything else 66 million years ago.
That story is now coming to light, thanks to an international collaboration that has been underway for four years.
The first findings of the Avian Phylogenomics Consortium are being reported nearly simultaneously in 23 papers--eight papers in a special issue this week of Science, and 15 more in Genome Biology, GigaScience and other journals.
The results are funded in part ...
An ancient meteorite and high-energy X-rays have helped scientists conclude a half century of effort to find, identify and characterize a mineral that makes up 38 percent of the Earth.
And in doing so, a team of scientists led by Oliver Tschauner, a mineralogist at the University of Las Vegas, clarified the definition of the Earth's most abundant mineral - a high-density form of magnesium iron silicate, now called Bridgmanite - and defined estimated constraint ranges for its formation. Their research was performed at the Advanced Photon Source, a U.S. Department of Energy ...
