My favorite cell 

Arguably every cell in your body matters, but which are the most interesting? The most mysterious, surprising or — yes— even the prettiest? These might seem impossible questions to answer, but when we asked several Stanford Medicine scientists to name their favorite cell and explain why, answers came easily — and ran the gamut.

With some creative license, we found that each of the cells listed could be assigned a range of attributes not out of place in a high school yearbook. But while some are easy to categorize — it seems obvious that “most ambitious” should be awarded to the stem cells that give rise to and maintain all the body’s tissues — other categories are more competitive.

Should “best dressed” go to the stately, meticulously organized cells of the inner ear, or to the starburst beauty of the brain’s Purkinje cells? “Most athletic” to the foot-soldier fibroblasts that do the heavy lifting to quickly form scars after injury, allowing our ancestors to sprint from danger or after prey? Or to the cells of the heart’s sinoatrial node responsible for the electrical pulse that triggers every one of the around 2.5 billion heartbeats we experience throughout our lives?

Some of the cells aren’t even human. A naturally occurring gut bacterium that digests fiber — usually from our diets, but it’s not above chowing down on our intestinal lining when dietary fiber is scarce: “most likely to succeed”? A single-celled organism with a dainty skirt that can transform into a shape-shifting multicellular colony at the drop of a hat: “most creative”?

But while there’s certainly room to quibble about each cell’s specific category, what’s clear is that every one of them deserves an overarching title of “researcher’s pet.” Each scientist spoke passionately about their favorite cell, often highlighting little-known facts or connections that have a vast impact on human evolution, development and health.

Choanoflagellates

Florentine Rutaganira, PhD

Assistant professor of biochemistry
and of developmental biology

“We call them sperm with skirts,” said Florentine Rutaganira of choanoflagellates — aquatic organisms that toggle between life as a single cell, scooping up and supping on bacteria with their distinctive collar surrounding a wiggly flagellum, and multicellular colonies that resemble tree-like chains, spherical rosettes and more.

“The cells themselves are really unique,” Rutaganira said. “As someone who had previously only had exposure to mammalian cells, when I first saw them under the microscope I was like, ‘This is the most insane thing I’ve ever seen.’”

Choanoflagellates are the closest living single-celled relatives to animals. An intriguingly large proportion of their relatively small genome is devoted to genes for protein kinases — molecules that play key intercellular signaling roles in mammals.

Rutaganira launched her lab last year with the aim of learning whether and how the receptor protein kinases, which straddle the cell membrane, coordinate the choanoflagellate’s ability to switch between one cell and many, and what that can tell us about how mammalian cells communicate.

Intriguingly, the shapes of colonies choanoflagellates form is governed by the type of bacteria to which they are exposed. “I’ve done this experiment probably 1,000 times,” Rutaganira said. “You cohabitate these single-celled organisms with a specific type of bacteria, and you come in the next morning to find a beautiful set of colonies. It never gets old.”

“Understanding this transition will give us better insight into what happens when things go wrong,” Rutaganira said. “Cancer is essentially a breakdown in intercellular communication, and protein kinases are often mutated in cancer. Choanoflagellates are a good model system for studying these complex processes in a lab setting. And they’re also cute.”

Bacteroides
thetaiotaomicron, or B. theta

Justin Sonnenburg, PhD

Professor of microbiology and immunology and the Alex and Susie Algard Endowed Professor

In the eyes of Justin Sonnenburg, B. theta is a magician. A magician in the form of a naturally occurring gut bacterium that munches on the indigestible fibers found in fruits, nuts and other carbohydrate-rich foods and transforms them into beneficial metabolites that keep our bodies running smoothly.

“There are probably hundreds or thousands of carbohydrate structures that we can’t digest on our own,” Sonnenburg said. “B. theta has many genes dedicated to digesting all sorts of fiber.”

But if we don’t eat enough fiber, the naturally occurring gut bacterium turns feral, feasting instead on the carbohydrate-rich mucus that lines the gut.

“Normally this lining keeps our gut microbes at a safe distance,” Sonnenburg said. “As they say, good fences make good neighbors. But when B. theta starts digesting this lining, it may lead to inflammation and cause the gut lining to become leaky. Eating plenty of plant-based dietary fiber helps keep B. theta from eating us.”

Sonnenburg studies the dynamics of the gut microbiome and whether diet or medical intervention can modulate its composition to prevent disease. B. theta was the first prominent gut bacterium to have its genome fully sequenced, in 2003, launching a full-scale study of the hundreds of bacterial species in our gut microbiome. Sonnenburg remembers the moment that B. theta’s effect on the gut first captured his attention.

“It was 1996, and I read a paper in Science showing that if you colonized germ-free mice with B. theta, the lining of the gut began to produce a carbohydrate called fucose, which B. theta would then eat. It was almost like it was gardening the lining of the gut for its own food,” Sonnenburg said. “This was one of a handful of studies around that time that made me think ‘This is beyond science fiction.’ It was amazing.”

Hair cells in the inner ear

Alan Cheng, MD

Professor of otolaryngology and the Edward C. and Amy H. Sewall Professor in the School of Medicine

Deep inside your ear, past your eardrum, inside the shell-like cochlea, about 15,000 hair cells stand at attention. These cells sense motion, vibration and sound. Without them we couldn’t hear our loved ones’ voices, balance on one foot or thrill to the acceleration of a fast car. And when they’re gone, they’re gone.

“These cells are found only in the inner ear, and they don’t regenerate naturally,” Alan Cheng said. “They are critical to how we interact with our environment.”

Genetics, certain drugs, noise and aging all take their toll on hair cells. Cheng studies genetic reprogramming techniques to stimulate hair cell regeneration.

“Early in my career I fell in love with how hearing works and learned how little we can do to treat hearing loss, and I realized, ‘Oh, it’s the loss of these cells that is the major hurdle.’ The interesting and fun part has been understanding how they work and what we can do to regenerate them.”

It doesn’t hurt that the cells themselves are strikingly beautiful.

“They look like rows of statues on a checkerboard,” Cheng said. “They stick straight up, all facing in the same direction. It’s very organized and precise. And the cells themselves are gorgeous and elegant, like something you might find in an art magazine.”

Trophoblasts

Michael Angelo, MD, PhD

Associate professor of pathology

Pregnancy is a tricky time. A fetus demands an ever-increasing amount of nutrients and blood flow from the mother. It also needs protection from a maternal immune system trained to attack genetically dissimilar cells.

Enter the trophoblast. These cells, with genetic material from both parents, arise from the outer layers of the developing embryo to form the placenta.

As pregnancy progresses, trophoblasts burrow deeply into the uterine lining to remodel the maternal arteries that provide blood to the placenta to increase blood flow but not pressure. And they somehow do so without provoking an immune attack.

“These are dynamic, genetically foreign cells unlike any other cells in the body,” Michael Angelo said. “They also contribute directly to two key properties of being human. The remodeling of these arteries is more extensive in humans than in nearly all other mammals and allows us to withstand the concentrated weight of a developing fetus when walking upright. The increased blood flow also allows for the longer gestations necessary to develop big brains before birth.”

The uniquely human invasiveness of human trophoblasts also has a link to cancer. “That’s what first got me hooked,” Angelo said.

“There’s a striking correlation between the invasiveness of the placenta and the types of cancer an organism is likely to develop. That connection is pretty crazy. These are dynamic, genetically foreign cells unlike any other cells in the body.”

Salmonella Typhi

Denise Monack, PhD

Professor of microbiology and immunology and the Martha Meier Weiland Professor in the School of Medicine

Most of us are familiar with the form of the Salmonella bacteria that cause severe food poisoning. While occasional nationwide produce recalls may have us side-eying our salad greens, there’s an even more cunning relative that is, thankfully, rare in the United States: Salmonella Typhi.

This species of the bacteria homes to and infects the lining of the gut where it spreads to deeper tissue, evading our immune systems and causing typhoid fever. Typhoid is endemic in India, Bangladesh and parts of Africa, and more than 200,000 people in the world die from it each year.

While some people experience a fever, abdominal pain and headaches that are hallmarks of the disease, others have no symptoms, unknowingly spreading the disease to others à la Typhoid Mary of New York in the early 1900s.

These silent spreaders harbor Salmonella Typhi in clumps of white blood cells called granulomas lodged in the lymph nodes near the gut.

Denise Monack first became interested in Salmonella Typhi in the 1990s. “It has evolved a lot of tricks to escape the immune system.”

One such trick allows it to not just survive being engulfed by immune cells called macrophages but also to thrive inside them, pulling and spinning biological levers and dials like a mad scientist to fashion a comfortable niche for itself inside these erstwhile killing machines.

“It is basically a tiny cell biologist, working from the inside of the macrophage,” Monack said. “It produces over 20 factors to manipulate existing biological pathways to its advantage. It’s a cool bug.”

Sinoatrial node cells

William Goodyer, MD, PhD

Assistant professor of pediatric cardiology and electrophysiology

Nestled in the upper wall of the right atrium of the heart is a dime-sized, comma-shaped cluster of cells with arguably the most important job in the body: generating the electrical impulse that initiates every heartbeat. But these sinoatrial node cells are devilishly hard to identify with the naked eye.

“Damage to the node cells can be due to genetics or aging or diseases like heart failure,” William Goodyer said. “But accidental damage during cardiac surgeries is not uncommon because surgeons can’t see it and are therefore forced to estimate the location of the heart’s conduction system.”

If the cells are damaged, the only recourse is to implant an artificial pacemaker to keep the heart beating and the blood pumping.

“Many groups are trying to figure out how to reproduce these cells in a laboratory so that, in the future, we can repair damage by implanting a new sinoatrial node,” Goodyer said.

But it’s also important to try to prevent damage in the first place. In 2019, Goodyer mapped the entire electrical conduction system of the heart and developed dyes that can illuminate node cells and help surgeons steer clear.

Sinoatrial node cells are biological chameleons. They share many features with neurons, including their ability to generate and conduct electricity, which enables them to control the rhythms of the heart. Their unique characteristics proved a siren call early in Goodyer’s career that he found impossible to ignore.

“I did my PhD research on the development of the pancreas,” Goodyer said. “But I fell in love with the rhythm of the heart as a pediatric cardiology fellow, and it changed the trajectory of my career. It’s a huge unmet medical need and a prime opportunity to help kids.”

Hematopoietic stem cell

Irving Weissman, MD

Professor of pathology and of developmental biology, the Virginia and D.K. Ludwig Professor in Clinical Investigation in Cancer Research, and founder of the Stanford Institute for Stem Cell Biology and Regenerative Medicine

Imagine a child’s drawing of a tree, trunk springing from the ground and larger limbs giving way to ever smaller branches and leaves. As an allegory for human development, the roots of the tree would represent a fertilized egg, the trunk is the embryonic stem cells.

Moving upward, the different branches can be thought of as the various organs and tissues in the body. Nestled in every fork are tissue-specific stem cells dedicated to developing and maintaining their tissue or organ.

Irving Weissman was a high school student in Montana in the 1950s when he began researching the biology of skin transplantation. How does the immune system identify and reject foreign cells? Where does the immune system even come from?

Decades of research, most at Stanford Medicine, led in the 1980s to Weissman’s identification and isolation in mice and humans of the hematopoietic stem cell — the stem cell that can develop into all types of blood cells.

These stem cells are special. Their line of descendants is vast, and the relationships among the branches are far more complicated than depicted in a child’s drawing. But Weissman dedicated his career to untangling these family ties to understand normal development and cancer — meticulously tracing back from leaf to branch to limb to trunk to identify the earliest mutations found in blood cancers like leukemia.

Weissman’s decades of discovery highlight the importance of tissue-specific stems cells and have laid the foundation for new treatments for cancer, blood diseases and organ rejection.

“Stem cell biology is just taking off,” Weissman said. “Every tissue has stem cells if you just look deeply enough. It’s 2024 and we are just starting to realize the full clinical impact of these early discoveries.”

“I always thought I should just follow my nose,” Weissman said, “and if you get a result that is a little unexpected, explore it. I didn’t start off focusing on hematopoietic stem cells, but I got there pretty fast. I was lucky.”

Purkinje cells

Jennifer Raymond, PhD

Professor of neurobiology and the Berthold and Belle N. Guggenhime Professor II

Science is primarily a visual medium. Researchers peer at cells through a microscope, pore over stacks of data and observe the behavior of laboratory animals. Jennifer Raymond does all that.

But she also gets to hear her favorite cells hard at work, their staticky cadence recorded through an electrode changing as the specialized neurons funnel electric impulses between the cerebellum and other brain areas.

“The cerebellum used to be thought of as controlling mostly motor skills, with the bulk of thinking and cognitive processing tasks assigned to the cerebral cortex,” Raymond said. “But recently our understanding of roles played by the cerebellum has just exploded — language, fear, anxiety, navigation, you name it.”

Perhaps not surprisingly, the cells are hyperactive compared with many of the brain’s neurons — firing off as many as 100 impulses per second.

They are also much larger and flatter than their peers, stacking their cell bodies atop one another to create an intricate — and, frankly, drop-dead gorgeous — signaling network of branching dendrites that gather input from about 100,000 to 200,000 other cells. In comparison, “normal” neurons hear from only about 10,000 other neurons.

“Because everything that happens in the cerebellum is funneled through Purkinje cells, we know we are collecting all the output from the cerebellum when we place an electrode in this hub,” Raymond said.

“It’s a simple circuit but, because it is highly evolutionarily conserved, we know it must reflect a fundamentally important type of computation and learning. It’s so exciting to hear how the frequency of these impulses increase or decrease in real time as an animal learns.”

Fibroblasts

Michael Longaker, MD

Professor of surgery and the Deane P. and Louise Mitchell Professor in the School of Medicine

“I call it scar wars,” said Michael Longaker, of his fascination with fibroblasts — cells that secrete the proteins that fill the spaces between cells in normal development and wound healing. In humans, the latter often leaves a scar that can interfere with a tissue’s normal function.

Humans are unique among mammals in their propensity to form large scars, but even that must be learned. Human embryos don’t scar after fetal surgeries until the last trimester of gestation — a fact that piqued Longaker’s interest as a postdoctoral scholar in the 1980s.

Over the decades, he has studied how fibroblasts make scars, and whether there is a way to prevent scarring or remodel existing scars into normal tissue.

“Fibroblasts sense many aspects of their environment, including mechanical forces,” Longaker said. “If we block that ability, we can heal without scarring.”

Overenthusiastic fibroblasts are responsible for fibrosis, which is the development of fibrous connective tissue in response to injury. Longaker estimates that nearly half of all deaths each year are caused by some form of fibrosis in the guise of heart disease, lung disease, liver cirrhosis and more.

“Fibroblasts are fascinating cells that most people ignore,” Longaker said. “In a way, they are foot soldiers, responding to physical and biological cues around them. But they have an enormous impact on human health.”