Cells are the fundamental unit of life.
There are over 37 trillion of them in the human body,
100 times more than the number of stars in the Milky Way.
So each of the cells in our tissues
fulfills a different type of role,
but together they like make this beautiful symphony
that lets the tissue maintain itself
and then lets our organs do their functions
and eventually our entire body.
Over the past 300 years,
we've learned what cells are made of,
how they function and divide into new cells.
But there's still a lot we don't know.
How many different cell types are there in the human body?
How do different cell types work together?
And how do changes in cells cause diseases?
About 2,000 researchers from over 70 different countries
are trying to answer these questions
by building a Human Cell Atlas,
a complete map of all the cell types in our body.
What we envision is that the Human Cell Atlas
will be a foundational reference for biomedical research
in many, many areas.
And it tells us something about ourselves,
about what our bodies are made of,
and also going to help us and many others
over time develop new medicines for patients.
So we like to think about the final atlas fondly
as a Google Map of the human body.
You could say, well, I want to understand the cells
in the nose, or the cells inside your mouth,
or the cells of the skin,
or the cells of this particular region in the brain.
And you could drill into that region.
First you could look at coarse resolution.
You would know how the tissue is ordered,
and then you could go in finer and finer resolutions
all the way to the level of individual cells.
Aviv Regev is the co-chair of Human Cell Atlas,
a 10-year endeavor to discover new cell types
as well as map them in detail.
The other way that we like to think about the atlas
is what we call the periodic table of the cells.
If you think about the periodic table of the elements,
it's not just a description of the elements.
It's also a theory of the elements.
You know, Mendeleev was able to predict
that elements would exist
before they were actually empirically found.
And one of the things that we hope will happen
with this atlas is that we will learn
how to better predict cells and their behaviors.
In 1664, around 200 years before Mendeleev
and his periodic table, English scientist Robert Hooke
discovered the existence of cells
when he put a piece of cork under a microscope.
Ever since then, microscopy has played an important role
in studying cell structure and function.
By looking at cells under a microscope
and studying their reactions
with chemical stains, which make them visible,
scientists identified about 300 cell types
in the human body.
But cells which look similar under a microscope
can sometimes turn out to be chemically different.
And so our knowledge has been limited until now.
Something happened a few years ago,
which was a major technological advance
that allows us to look at the molecular content
of the individual cells
through their RNA molecules in particular.
And we call this single-cell genomics.
In the past, we take say a piece of tissue
that would have many different kinds of cells in it.
And we would put it basically
through the lab equivalent of a blender.
And so if you think of every cell
as a different piece of fruit,
there's blueberries and strawberries
and raspberries and kiwis and so on,
then what you get as a result of that is very similar
to a fruit smoothie.
It's a blend of all of the molecular contents
of all of those cells
and you get to measure the average.
That is not a great way by which to discover
what are the individual cells.
What single-cell genomics allows us to do
is look at every individual cell
in the molecules within it separately.
And so this gives us basically the equivalent
of a fruit salad.
Now you can see each individual piece of strawberry
and blueberry and kiwi and raspberry.
Where the workflow starts is with acquiring the tissue.
And so in that case there are biopsies
from deceased transplant donor tissue.
The biopsy tissue is broken down
into single whole cells.
These individual cells are loaded
onto a microfluidic droplet robot,
which carries out the chemical reactions
needed to prepare them for sequencing.
We're measuring which genes are switched on in each cell.
To understand why single-cell
sequencing is important,
we need to understand a little bit about how cells work.
Our genome, which is made of DNA,
is the instruction manual for the cells in our body.
Within this genome are thousands of different genes,
which each code a different protein.
These proteins are made using a chemical called RNA.
By using single-cell sequencing,
if you can identify which genes
each individual cell is using,
you can tell what sort of cell it is.
But there's one problem.
We have about 25,000 different genes in our genome.
And with single-cell genomics,
we can measure several thousand per cell.
And so what the technology is telling us
is in each single cell which specific subset
of 2,000 or 3,000 genes is switched on in that single cell
out of the 25,000 possible.
For every single cell, you have several thousand genes
expressed and you can have hundreds of thousands of cells.
So the data matrix is hundreds of thousands
multiplied by thousands of data points.
So we really are talking about sizes of data
that are getting close to astronomical.
With the help of machine learning
and artificial intelligence,
these huge amounts of data can be processed and analyzed,
eventually leading to the discovery of new cell types.
The Human Cell Atlas community has been able to reveal
dozens, maybe now up to even a hundred,
different new cell types
across different tissues of the body.
So for example, several years ago
together with my colleagues,
we did a study of the airways in the lungs
and we discovered a new cell type,
which is very rare and that nobody knew existed.
It was literally not there until we discovered it.
Of course it was in our lungs,
but it was not in our knowledge.
And that cell type that we call the ionocyte
ended up being especially exciting for us.
Because it uses, it expresses very highly
the gene known as CFTR, or the cystic fibrosis gene.
And until we discovered this very rare cell type,
scientists actually assumed that this gene
is used by other cells in the lung and the airways.
And it turns out that it is not used by those cells.
It is used by these super rare cells
that we didn't know existed.
Cystic fibrosis is a fatal hereditary disease
that affects the lungs and digestive system.
The discovery of this new cell type
could help diagnose and treat the disease.
Our hope is that this would allow us
to also understand disease better.
Because what happens in disease is that cells
all of a sudden misbehave.
They don't do the things that they're supposed to do.
And what we want to develop
are the right kinds of medicines of course
that would bring them back to their native state.
And we hope that the atlas would be a foundational
reference and resource like the human genome has been
in order to help scientists both understand
basic biology and understand disease.
Individual cell types identified
using single-cell sequencing
can then be located within tissue samples
to make a detailed 3D map.
So far over 39 million cells have been analyzed,
covering specific organs, such as the brain, skin and lungs.
But to make a complete cell atlas covering every tissue,
organ and system in the human body,
billions more cells need to be analyzed.
It is a crazy quest and it's ridiculously ambitious,
but we have these little milestones along the way.
And each time we discover something new,
there's an incredible excitement and thrill.
And that keeps us going as well.