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stem cells

Modeling Hypertrophic Cardiomyopathy in a Dish

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Image of cardiac fibers

Credit: Zhen Ma, University of California, Berkeley

Researchers have learned in recent years how to grow miniature human hearts in a dish. These “organoids” beat like the real thing and have allowed researchers to model many key aspects of how the heart works. What’s been really tough to model in a dish is how stresses on hearts that are genetically abnormal, such as in inherited familial cardiomyopathies, put people at greater risk for cardiac problems.

Enter the lab-grown human cardiac tissue pictured above. This healthy tissue comprised of the heart’s muscle cells, or cardiomyocytes (green, nuclei in red), was derived from induced pluripotent stem (iPS) cells. These cells are derived from adult skin or blood cells that are genetically reprogrammed to have the potential to develop into many different types of cells, including cardiomyocytes.

Study Shows Genes Unique to Humans Tied to Bigger Brains

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cortical organoid

Caption: Cortical organoid, showing radial glial stem cells (green) and cortical neurons (red).
Credit: Sofie Salama, University of California, Santa Cruz

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.

Creative Minds: Programming Cells to Write Their Own Memoirs

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MEMOIR cells

Caption: MEMOIR cells variably activate (cyan). The recorded information is then read out to visualize certain RNA transcripts (red).
Credit: Elowitz and Cai Labs, Caltech, Pasadena, CA

One of the most fascinating challenges in biology is understanding how a single cell divides and differentiates to form a complex, multicellular organism. Scientists can learn a lot about this process by tracking time-lapse images through a microscope. But gazing through a lens has its limitations, especially in the brain and other opaque and inaccessible tissues and organs.

With support from a 2017 NIH Director’s Transformative Research Program, a California Institute of Technology (Caltech) team now has a way around this problem. Rather than watching or digging information out of cells, the team has learned how to program cells to write their own molecular memoirs. These cells store the information right in their own genomic hard drives. Even better, that information is barcoded, allowing researchers to read it out of the cells without dissecting tissue. The programming can be performed in many different cell types, including stem or adult cells in tissues throughout the body.

Snapshots of Life: The Birth of New Neurons

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Radial Glia in Oil

Credit: Kira Mosher, University of California, Berkeley

After a challenging day at work or school, sometimes it may seem like you are down to your last brain cell. But have no fear—in actuality, the brains of humans and other mammals have the potential to produce new neurons throughout life. This remarkable ability is due to a specific type of cell—adult neural stem cells—so beautifully highlighted in this award-winning micrograph.

Here you see the nuclei (purple) and arm-like extensions (green) of neural stem cells, along with nuclei of other cells (blue), in brain tissue from a mature mouse. The sample was taken from the subgranular zone of the hippocampus, a region of the brain associated with learning and memory. This zone is also one of the few areas in the adult brain where stem cells are known to reside.

Snapshots of Life: Growing Mini-Brains in a Dish

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Brain grown in a lab dish

Credit: Collin Edington and Iris Lee, Department of Biomedical Engineering, MIT

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.

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