New techniques let scientists zero in on individual cells

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AP
ID: 
1551680565439715900
Mon, 2019-03-04 09:34

NEW YORK: Did you hear what happened when Bill Gates walked into
a bar? Everybody there immediately became millionaires — on
average.
That joke about a very rich man is an old one among statisticians.
So why did Peter Smibert use it to explain a revolution in
biology?
Because it shows averages can be misleading. And Smibert, of the
New York Genome Center, says that includes when scientists are
trying to understand the basic unit of life, the cell.
Until recently, trying to study key traits of cells from people and
other animals often meant analyzing bulk samples of tissue,
producing a mushed-up average of results from many cell types. It
was like trying to learn about a banana by studying a
strawberry-blueberry-orange-banana smoothie.
In recent years, however, scientists have developed techniques that
let them directly study the DNA codes, the activity of genes and
other traits of individual cells. The approach has become widely
adopted, revealing details about the body that couldn’t be shown
before. And it has opened the door to pursuing an audacious goal:
listing every cell type in the human body.
“Single-cell analysis is crucial for a comprehensive
understanding of our biology and health,” Dr. Francis Collins,
the director of the National Institutes of Health, declared
recently.
In fact, the journal Science named the techniques that allow
single-cell tracking of gene activity over time in developing
organisms and organs as its “breakthrough of the year” for
2018. Its announcement declared, “The single-cell revolution is
just starting.”
Even complicated animals like us are really just massive
communities of cells, each taking on a particular role and working
with its neighbors. An average adult human has 37 trillion or so of
them, and they’re surprisingly varied: the inner lining of the
colon, for example, has more than 50 kinds of cells.
It was just five years ago that methods for decoding of DNA and its
chemical cousin RNA from individual cells became broadly
accessible, according to the journal Nature Methods. New techniques
are still being developed to pry more and more secrets out of
individual cells.
The single-cell approach is leading to a slew of discoveries. In
just the past year, for example:
— Scientists closely tracked gene activity within fish and frog
embryos, a step toward the longstanding goal of understanding how a
single fertilized egg can produce an animal. One study compiled
results from more than 92,000 zebrafish embryonic cells.
— Other researchers revealed details of the physical connection
between pregnant women and the fetus, giving potential clues for
understanding some causes of stillbirth.
— A study found a pattern of gene activity in some melanoma cells
that let them resist immunotherapy, the practice of unleashing the
body’s immune system on cancer. That might lead to finding a way
to render those cells vulnerable.
And a pair of other studies may affect research into cystic
fibrosis, the genetic disease that causes lung infections and
limits breathing ability. Scientists have long known that the
disease stems from a faulty version of protein called CFTR. The
studies identified a type of rare cell in the airway that makes
large amounts of CFTR, surpassing earlier but only dimly understood
indications that such cells existed.
The discovery offers great potential for guiding the development of
new treatments, said Dr. William Skach, senior vice president of
research affairs for the Cystic Fibrosis Foundation. Single-cell
techniques will be important in studying them further for coming up
with new therapies, he said. (Two co-authors of one paper are from
the foundation).
At the MD Anderson Cancer Center of the University of Texas,
Nicholas Navin uses single-cell DNA studies to reveal different
patterns of mutations in various cells of a single tumor. That lets
him reconstruct when and where those mutations appeared as the
tumor evolved from benign cells. And he can identify cells that
contain combinations of mutations that make them the most
lethal.
Someday, such research should indicate what treatments to use for
particular patients, or which patients have the highest risk of the
disease progressing, he says. It might also allow doctors to check
how well their treatments are working against a cancer over time. A
decade or two from now, it might let doctors detect cancers very
early by picking up and analyzing the DNA of rare cells in blood
tests, he says.
Meanwhile, the ability to produce single-cell results for hundreds
of thousands of cells at a time has opened the door to a huge
effort to catalog every cell type in the human body. More than
1,000 scientists from 57 countries have joined the Human Cell Atlas
Consortium, which estimates it will eventually profile at least 10
billion cells found in both healthy and sick people.
Why do this? It’s a natural follow to the big project that
catalogued all the human genes, says co-organizer Aviv Regev, a
biology professor at the Massachusetts Institute of Technology and
researcher at the Broad Institute of MIT and Harvard. (Her salary
is paid by the Howard Hughes Medical Institute, which also supports
The Associated Press Health & Science Department.)
The gene map led to identifying thousands of genetic variants that
raise or lower the risk of many diseases. But to turn that into
therapies, scientists have to know in which cells those variants
act, she said. And to run down those cells in the human body, “we
have to map all of them.”
Some cells are rarer than others, but these can be just as critical
for a functioning body as their more plentiful neighbors, she
said.
She hopes for a first draft of the cell atlas in about five years,
focused on certain organs and tissues of the body. To finish the
job might take about a decade, she figures. Regev won’t hazard a
guess about how many cell types will be found for the entire human
body.
“This is not going to cure all disease immediately,” she said,
but “it is a critical stepping stone.”

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New techniques let scientists zero in on individual cells