In seeking the biological answer to the question of what it means to be human, the brain’s cerebral cortex is a good place to start. This densely folded, outer layer of grey matter, which is vastly larger in Homo sapiens than in other primates, plays an essential role in human consciousness, language, and reasoning.
Now, an NIH-funded team has pinpointed a key set of genes—found only in humans—that may help explain why our species possesses such a large cerebral cortex. Experimental evidence shows these genes prolong the development of stem cells that generate neurons in the cerebral cortex, which in turn enables the human brain to produce more mature cortical neurons and, thus, build a bigger cerebral cortex than our fellow primates.
That sounds like a great advantage for humans! But there’s a downside. Researchers found the same genomic changes that facilitated the expansion of the human cortex may also render our species more susceptible to certain rare neurodevelopmental disorders.
Posted In: News
Tags: autism, Autism Spectrum Disorder, brain, cerebral cortex, cortical neurons, CRISPR/Cas9, DNA sequencing, duplication, evolution, gene-editing technology, genes, genomics, human genome, Human Genome Project, humans, macrocephaly, microcephaly, microdeletion, neurodevelopmental disorders, neurons, neuroscience, Notch, organoids, primates, radial glial stem cells, schizophrenia, signaling genes, stem cells
Something pretty incredible happens—both visually and scientifically—when researchers spread neural stem cells onto a gel-like matrix in a lab dish and wait to see what happens. Gradually, the cells differentiate and self-assemble to form cohesive organoids that resemble miniature brains!
In this image of a mini-brain organoid, the center consists of a clump of neuronal bodies (magenta), surrounded by an intricate network of branching extensions (green) through which these cells relay information. Scattered throughout the mini-brain are star-shaped astrocytes (red) that serve as support cells.
Tags: 2017 Koch Institute Image Awards, Alzheimer’s disease, astrocytes, brain, brain in a dish, confocal laser scanning microscope, human on a chip, human physiome, hydrogel, induced Pluripotent Stem cells, mini brain, neuronal bodies, organoids, physiome, stem cells, The Koch Institute Galleries, tissue chips
Caption: This “spooky” video ends with a scientific image of intestinal crypts (blue and green) plus organoids made from cultured crypt stem cells (pink).
As Halloween approaches, some of you might be thinking about cueing up the old TV series “Tales from the Crypt” and diving into its Vault of Horror for a few hours. But today I’d like to share the story of a quite different and not nearly so scary kind of crypt: the crypts of Lieberkühn, more commonly called intestinal crypts.
This confocal micrograph depicts a row of such crypts (marked in blue and green) lining a mouse colon. In mice, as well as in humans, the intestines contain millions of crypts, each of which has about a half-dozen stem cells at its base that are capable of regenerating the various types of tissues that make up these tiny glands. What makes my tale of the crypt particularly interesting are the oval structures (pink), which are organoids that have been engineered from cultured crypt stem cells and then transplanted into a mouse model. If you look at the organoids closely, you’ll see Paneth cells (aqua blue), which are immune cells that support the stem cells and protect the intestines from bacterial invasion.
A winner in the 2016 “Image Awards” at the Koch Institute Public Galleries, Massachusetts Institute of Technology (MIT), Cambridge, this image was snapped by Jatin Roper, a physician-scientist in the lab of Omer Yilmaz, with the help of his MIT collaborator Tuomas Tammela. Roper and his colleagues have been making crypt organoids for a few years by placing the stem cells in a special 3D chamber, where they are bathed with the right protein growth factors at the right time to spur them to differentiate into the various types of cells found in a crypt.
Once the organoids are developmentally complete, Roper can inject them into mice and watch them take up residence. Then he can begin planning experiments.
For example, Roper’s group is now considering using the organoids to examine how high-fat and low-calorie diets affect intestinal function in mice. Another possibility is to use similar organoids to monitor the effect of aging on the colon or to test which of a wide array of targeted therapies might work best for a particular individual with colon cancer.
Video: Gut Reaction (Jatin Roper)
Jatin Roper (Tufts Medical Center, Boston)
Omer Yilmaz (Massachusetts Institute of Technology, Cambridge)
NIH Support: National Cancer Institute; National Institute on Aging
Tags: art, BioArt, colon, colon cancer, crypts, crypts of Lieberkühn, diet, high-fat diet, intestinal crypts, intestine, low-calorie diet, organoids, Paneth cells, stem cells, The Koch Institute Galleries
When Nancy Allbritton was a child in Marksville, LA, she designed and built her own rabbit hutches. She also once took apart an old TV set to investigate the cathode ray tube inside before turning the wooden frame that housed the TV into a bookcase, which, by the way, she still has. Allbritton’s natural curiosity for how things work later inspired her to earn advanced degrees in medicine, medical engineering, and medical physics, while also honing her skills in cell biology and analytical chemistry.
Now, Allbritton applies her wide-ranging research background to design cutting-edge technologies in her lab at the University of North Carolina, Chapel Hill. In one of her boldest challenges yet, supported by a 2015 NIH Director’s Transformative Research Award, Allbritton and a multidisciplinary team of collaborators have set out to engineer a functional model of a large intestine, or colon, on a microfabricated chip about the size of a dime.
Tags: 2015 NIH Director’s Transformative Research Award, bioengineering, colon, colon on a chip, crypts, diet, digestion, gastrointestinal disease, gastrointestinal tract, genomics, hydrogel, immunity, intestinal crypt, intestine, large intestine, microbiome, organoids, regenerative medicine, simulacrum, stem cell technology, stem cells, tissue chips
In response to the health threat posed by the recent outbreak of Zika virus in Latin America and its recent spread to Puerto Rico and Florida, researchers have been working at a furious pace to learn more about the mosquito-borne virus. Considerable progress has been made in understanding how Zika might cause babies to be born with unusually small heads and other abnormalities and in developing vaccines that may guard against Zika infection.
Still, there remains an urgent need to find drugs that can be used to treat people already infected with the Zika virus. A team that includes scientists at NIH’s National Center for Advancing Translational Sciences (NCATS) now has some encouraging news on this front. By testing 6,000 FDA-approved drugs and experimental chemical compounds on Zika-infected human cells in the lab, they’ve shown that some existing drugs might be repurposed to fight Zika infection and prevent the virus from harming the developing brain . While additional research is needed, the new findings suggest it may be possible to speed development and approval of new treatments for Zika infection.
Tags: Aedes mosquito, birth defects, CDK inhibitors, drug repurposing, drug screening, Ebola virus, emiricasan, microcephaly, mosquito, neural progenitor cells, niclosamide, organoids, PHA-690509, repurposing drugs, small-molecule inhibitors, vaccine, virology, Zika, Zika vaccine, Zika virus