Small Intros to Big Questions: How many types of cells make up a human?

The average human body is made up of 37 trillion cells — that’s roughly 4.3 million times the population of New York City. This cellular world is vastly diverse, and biologists are constantly discovering new types of cells with novel functions. But what exactly makes one cell type different from another? How many different kinds of cells comprise a person? Is it possible to change one type of cell into another?

Before we delve into those questions, we need to review a little cell and molecular biology. Complex life is multicellular, meaning that many cells cooperate to make a functioning organism. In most cases, the cells that comprise these conglomerates have specialized over the course of evolution, taking on tasks that are unique from the other cells in the organism. Much like what happened during the development of human societies, this division of labor increases the efficiency of the entire organism.

For example, the neurons in your brain have particular features that allow them to quickly relay electrical information across the body. They send thin projections through your cranium, rocketing waves of electrical charge down to cells waiting at the other end. But, the cells that make up the lining of your gut have no such projections. Instead, they have special structures that pump nutrients from your intestine into your bloodstream. Cells in your inner ear can sense changes in pressure brought about by sound waves, and populations of cells in your scalp pump out Herculean amounts of a protein called keratin to build strands of hair. You function well because of the combined action of a huge array of different cell types.

You function well because of the combined actions of a huge array of different cell types.

What makes a cell a certain “type”?

Much like you’d be able to identify a scientist by her pipettes, we identify cell types by the tools they use to do their jobs. These tools are largely made of proteins – molecular machines that contract, pump, or move cargo around. The information needed to build these proteins is encoded in genes, which are made up of DNA. Genes are complex informational units, containing not only the instruction manuals for building proteins, but also stretches of sequence that can amplify or dampen how much of the protein is produced. It’s this regulatory capacity of DNA that allows different cells to build unique combinations of protein tools.

So, even though every cell in your body carries exactly the same DNA, the tracts of sequence that are chosen to build protein tools differ between cell types. Thus, cell types are determined by differential expression of genes.

Want to explore the diversity of cell types?  Check out The Cell Image Library ! They curate stunning images of a huge variety of cells for your perusal.

How do cells express different sets of genes?

The genes a particular cell expresses, and therefore what protein tools it builds and what type of cell it becomes, are decided by two processes, operating on two timescales. Over evolutionary time, natural selection shapes which genes are available to a given cell. Random mutations in DNA that happen to make a particular protein a little bit better, or confer upon it an entirely new function, change an organism’s library of potential cellular tools. Genes can also be acquired or lost by more dramatic mechanisms, but that’s a topic for a different post.

But how do cells within the same animal, and therefore possessing the same DNA, differentiate from each other? The answer lies in sophisticated mechanisms for selectively reading out particular regions of DNA, and ignoring others. There are proteins, called transcription factors, that surveil DNA in search of specific sequences. Once found, they nudge the cell towards building more of the proteins encoded in those sequences. There are also proteins that fold DNA into tight balls, barring access to the folded regions. The combined action of these two forces – which encourage the production of particular proteins and repress the production of others, allow cells that carry the same DNA sequence to build unique suites of protein components.

Early in development, an animal embryo is made up of cells that have yet to specialize. Over time, they experience a combination of transcription factors that influence which proteins they’ll be able to build later. For example, expression of transcription factor A early in development might increase the expression of transcription factor B which goes on to increase the expression of transcription factor C, and so on and so forth. Each transcription factor in the chain influences the expression of numerous other genes. Therefore, the history of transcription factor expression confines which proteins a cell will be able to build throughout its life. The British developmental biologist Conrad Hal Waddington (a fascinating character, worthy of a Google) developed a nice visual depiction of this idea. In his “epigenetic landscape” a cell starts out on high a hill, and over the course of development, rolls down into one of many possible grooves, corresponding to unique fates. These grooves are defined by the history and current expression of genes, and once you’re in a groove, you can’t cheat gravity and roll back up the hill to change course.

Waddington-epigenetic-landscape-In-this-metaphor-the-undifferentiated-embryonic
Waddington conceived of the “epigenetic landscape”; a handy tool to intuit how cell fate is increasingly bounded over time, as cells “roll” downhill to more differentiated states. Image credit: Maximino Aldana.

Can a cell change from one type to another?

 Let’s explore that feature of Waddington’s landscape – the idea that once cells take on a particular fate, they can’t go back and change. Until the end of the 20th century, it was assumed that once fated, a cell’s identity was set in stone. However, the field was revolutionized in 2006 by the finding that, if bathed in particular soup of transcription factors, fated cells can in fact roll back up the hill to become less determined. Incredibly, you only need to add a few “master” transcription factors to reset the gene expression of a cell to a less differentiated state. Then, you can add a soup of more specific transcription factors in order to coax the newly undifferentiated cells back towards different fates of your choosing. The process is a bit labor intensive, but incredibly important, illustrating how central transcription factors are in dictating the identity of a cell, and allowing scientists to avoid using embryonic stem cells when studying the establishment of cell fates.

Why is understanding cell types important?

Technological advancements in the last ten years have allowed more and more biologists to probe all of the genes being expressed in every cell in an animal (if you’re interested in this, check out my previous FACS post, or this post or this paper). This mind-boggling wealth of data has uncovered a number of cell types entirely new to science! Many of these newly-discovered cell types carry out important jobs that were once mysterious to biologists, and are good targets for therapeutics. Plus, our job as biologists is to shed some light on the complexity of living things – understanding the diversity of cellular life is part of that task.

 Finally, how many types of cells make up a human?

We don’t know! Best estimates hover around 200, but that number is likely to grow as scientists develop better tools for carrying out cellular censuses.

**** an important footnote about agency: It’s easiest to understand the behavior of biological systems by ascribing some agency to cells, genes, or organisms. But in fact, cells don’t “choose” which genes to express, and proteins aren’t “built” with a specific function in mind. All of what I’ve described is the insanely complex product of millions of years of accidents – random mutations and cellular collaborations and DNA swapping – that have been chiseled by the relentless selection pressure of evolution to produce a vast diversity of self-assembling biological machines. There’s no directionality or greater purpose or real reason for why cells do what they do, which makes it all the more incredible!

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