A new color-coding tool is enabling scientists to better track live blood stem cells over time, a key part of understanding how blood disorders and cancers like leukemia arise, report researchers in Boston Children’s Hospital’s Stem Cell Research Program.
In Nature Cell Biology today, they describe the use of their tool in zebrafish to track blood stem cells the fish are born with, the clones (copies) these cells make of themselves and the types of specialized blood cells they give rise to (red cells, white cells and platelets). Leonard Zon, MD, director of the Stem Cell Research Program and a senior author on the paper, believes the tool has many implications for hematology and cancer medicine since zebrafish are surprisingly similar to humans genetically. …
To the eye, nervous systems look like a tangled mess of neurons and their tree-like branches known as dendrites, but it’s really organized chaos. How the system finds order has intrigued but eluded scientists. In the worm C. elegans, Max Heiman, PhD and graduate student Candice Yip found an elegant system to help explain how neurons each maintain their own space.
Normally, worms have just one neuron of a certain type on either side of their bodies. Yip did a “forward genetic screen” — mutating genes at random to find factors important for neuron wiring. One mutation caused the worm to grow not one set of neurons but five. By engineering the neurons to make a color-changing signal — as shown above — Yip showed that these extra neurons didn’t overlap with each other, but instead carved out discrete territories — a phenomenon known as tiling. How?
Acting on a hunch, Yip and Heiman, of Harvard Medical School and Boston Children’s Hospital’s Division of Genetics and Genomics, showed that C. elegans, faced with an increase in neurons, pressed a molecule called netrin into service to enforce boundaries between them. Netrin is better known for helping nerve fibers navigate to their destinations. When Yip took netrin out of action, the dendrites from the five neurons crossed the invisible borders and grew entangled.
The findings, published today in Cell Reports, could provide insight into neuropsychiatric diseases, believes Heiman, also part of Boston Children’s F.M. Kirby Neurobiology Center. “It’s fundamental to neuropsychiatric disease to make sure brain wiring goes right,” he says. “This is also story about how new features evolve, and how you can form something as complicated as a nervous system. There are pathways that bring everything into order.”
Type 1 diabetes afflicts more than 300 million people worldwide. Researchers have long sought a way to replace the insulin-producing beta cells lost in the disease, but transplanted cells are susceptible to immune attack. In this image, beta cells generated from human embryonic stem cells are encapsulated in microspheres made from a material called alginate, which help cloak the cells from the immune system. However, the reddish, blue and green markers on the spheres’ surfaces indicate that immune cells have discovered spheres and their cargo, and begun to block them off from the rest of the body.
In simultaneous papers in Nature Medicine and Nature Biotechnology, Daniel Anderson, PhD — a professor of applied biology at MIT and a researcher in Boston Children’s Hospital’s Department of Anesthesia, Perioperative and Pain Medicine — and his collaborators reported on their search for effective cloaking materials They also announced that microsphere-encapsulated beta cells can reverse diabetes in a mouse model. With further work on the microspheres’ chemistry and geometry, the team hopes to improve their cloaking abilities and provide longer lasting protection for beta cells. (Image: Andrew Bader, Omid Veiseh, Arturo Vegas, Anderson/Langer Laboratory, Koch Institute at MIT)
Once they detect an invader, inflammasomes send out signals that trigger infected cells to die using an inflammatory death pathway called pyroptosis. They also call for backup from the adaptive immune system, in the form of inflammation. (Image: Wu laboratory/Liman Zhang)
Cerebral palsy (CP) is the most common motor disability of childhood. The brain injury causing CP disrupts touch perception, a key component of motor function. In this brain image from a child with CP (click to enlarge), the blue lines show nerve fibers going to the sensory cortex. The colored cubes at the top represent the parts of the sensory cortex receiving touch signals from the thumb (red cube), middle finger (blue) and little finger (green). An injury in the right side of the brain (dark area) has reduced the number of nerve fibers on that side, reducing touch sensation in the left hand and resulting in weakness.
Oral squamous cell carcinoma (OSCC), a kind of oral cancer, affects some 30,000 Americans annually. It spreads through the lymphatic system and often has already metastasized by the time it’s diagnosed. The top image here, from a recent study in the American Journal of Pathology, is a healthy mouse tongue; the bottom is the swollen tongue of a mouse with OSCC. The cancerous tongue is overloaded with lymphatic vessels, appearing in blue and white, which help the tumor spread to the regional lymph nodes. The Bielenberg lab in Boston Children’s Hospital’s Vascular Biology Program is studying ways of blocking the progression of this and other cancers by inhibiting their spread through the lymphatic system. (Image: Bielenberg laboratory/Kristin Johnson)