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  • 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.

Cells are the fundamental unit of life.

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Building the Ultimate Map of the Human Body

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    joey joey posted on 2021/06/15
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