4. Working in twin 4-hour shifts each day, Sulston
would train a light microscope on a single
Caenorhabditis elegans embryo and sketch what he
saw at 5-minute intervals, as a fertilized egg
morphed into two cells, then four, eight and so on.
He worked alone and in silence in a tiny room at the
Medical Research Council Laboratory of Molecular
Biology in Cambridge, UK, solving a Rubik's cube
between turns at the microscope.
“I did find myself little distractions,” the
retired Nobel prize-winning biologist once recalled.
5.
6. His hundreds of drawings revealed the rigid
choreography of early worm development,
encompassing the births of precisely 671 cells,
and the deaths of 111 (or 113, depending on the
worm’s sex).
Sulston and his collaborators were able to draw
up the first, and so far the only, complete ‘cell-
lineage tree’ of a multicellular organism
7. No one could ever track the fates of
billions of cells in a mouse or a human
with just a microscope and a Rubik’s cube
to pass the time.
But there are other ways.
Revolutions in biologists’ ability
to edit genomes and sequence
them at the level of a single cell
have sparked a renaissance in
cell-lineage tracing.
8. Fast forward a decade, and researchers have
developed a suite of powerful tools to probe
the biology of lone cells, from their RNA
molecules and proteins to their individual and
unique genomes. Now, he envisions a way of
capturing the developmental course of a
human, frame by frame, from fertilized egg to
adult.
10. The cell is the basic unit of life and she
had long been looking for ways to
explore how complex networks of genes
operate in individual cells, how those
networks can differ and, ultimately, how
diverse cell populations work together.
During the days of 2011
How many types of cell in human body ?
11. ‘Sequenced the RNA of 18 seemingly
identical immune cells from mouse bone
marrow, and found that some produced
starkly different patterns of gene
expression from the rest. They were
acting like two different cell subtypes’
12. That made Regev want to push even further: to
use single-cell sequencing to understand how
many different cell types there are in the human
body, where they reside and what they do.
Her lab has gone from looking at 18 cells at a
time to sequencing RNA from hundreds of
thousands — and combining single-cell analyses
with genome editing to see what happens when
key regulatory genes are shut down.
13. The results are already widening the
spectrum of known cell types —
identifying, for example, two new forms
of retinal neuron — and Regev is eager to
find more.
In late 2016, she helped to launch the
International Human Cell Atlas, an
ambitious effort to classify and map all of
the estimated 37 trillion cells in the human
body
14.
15.
16. The project aims to discover and
characterize all the possible cell states in
the human body — mature and immature,
exhausted and fully functioning — which
will require much more sequencing.
17. Scientists have assumed that there are about 300 major
cell types, but Regev suspects that there are many more
states and subtypes to explore.
The retina alone seems to contain more than 100 subtypes
of neuron, Regev says.
Currently, consortium members whose labs are already
working on immune cells, liver and tumours are coming
together to coordinate efforts on these tissues and organs.
“This is really early days”
18. In co-coordinating the Human Cell Atlas
project, Regev has wrangled a committee
of 28 people from 5 continents and helped
to organize meetings for more than 500
scientists.
19. It was an otherwise
normal day in November
when Madeline
Lancaster
realized that she had
accidentally grown a
brain.
20. For weeks, she had been trying to get human
embryonic stem cells to form neural rosettes,
clusters of cells that can become many different
types of neuron.
But for some reason her cells refused to stick to the
bottom of the culture plate. Instead they floated,
forming strange, milky-looking spheres.
21. That day in 2011, however, she spotted an odd dot
of pigment in one of her spheres. Looking under
the microscope, she realized that it was the dark
cells of a developing retina, an outgrowth of the
developing brain.
And when she sliced one of the balls open, she
could pick out a variety of neurons.
Lancaster realized that the cells had assembled
themselves into something unmistakably like an
embryonic brain
22. These bits of tissue, called organoids because
they mimic some of the structure and function of
real organs, are furthering knowledge of human
development, serving as disease models and drug-
screening platforms, and might eventually be used
to rescue damaged organs.
“It's probably the most significant development in
the stem-cell field in the last five or six years”
says Austin Smith, director of the Wellcome Trust/MRC Stem Cell Institute at
the University of Cambridge, UK.
23. The current crop of organoids isn't perfect.
Some lack key cell types; others imitate only the
earliest stages of organ development or vary from
batch to batch.
So researchers are toiling to refine their organoids —
to make them more complex, more mature and more
reproducible.
Still, biologists have been amazed at how little
encouragement cells need to self-assemble into
elaborate structures.
“We just let the cells do what they want to do, and
they make a brain.” stem-cell biologist Jürgen Knoblich says
