good afternoon everyone let’s start with
a question to the audience what do you
think is the first cause of death in the
world well I hope you’re not thinking to
cancel that your reading at this light
because in fact it’s ischemic heart
disease its chemical diseases you’re
normally defined as a heart attack it’s
a first cause of death for men and women
and this hasn’t changed for the last 25
years
despite reduction of risk factors I’m
not telling you to start smoking stop
exercising and an LC diet in fact the
reason for this high frequency is the
aging of the population in the more rich
countries and in the poorer countries
people are moving to the cities changing
lifestyle and that brings in more cases
and more heart attacks let’s make sure
that you know what happens during a
heart attack
during a heart attack there is a sudden
loss of the blood flow to an area of the
heart muscles so what happens is you
have a big patch a injured part where
the cardiac muscle cells die now these
days were quite lucky because there are
a number of therapies to counteract and
save our lives
we got clot-busting drugs we got
interventional cardiologists that can
put in a stent into your blood vessels
and restore the blood flow so now 70% of
patients that have a heart attack will
survive however there are a 20 25 % of
people that will develop heart failure
now what is our failure heart failure is
a condition when the heart can not pump
any more efficiently the blood so you
get less blood to your brain to your
muscles you get tired you can think well
and so on the disease is quite serious
it cost a lot of money cost over 100
billion dollars per year globally and
what happens is when you get to the
later stage of the disease the only cure
is heart transplantation this is
obviously not for everyone now why do we
get heart failure well one of the
reasons is that we are not this little
cube monster we’re not axolotls so if
you cut the limb of this little monster
it would regrow if you cut his heart it
will regrow similar happens in the
zebrafish and somewhat surprisingly even
in the heart of neonatal mice just in
the few days of life though what happens
in the human heart well the human heart
is a bit more lazy a little bit more
boring just yet think of this when you
have a scratch in your hand
how long does it take for this king to
regrow and Bri he’ll just a matter of
days well the heart in the heart only
less than 1% to the cardiac muscle cells
regenerate in a whole year so the heart
is very lazy as I said and I mentioned
cardiac muscle cells look at it’s
beautiful organ this is a heart and it’s
made of many or these functional units
that are called cardiac muscle cells or
cardiomyocytes look how beautiful they
are every time I look down a microscope
I get so excited especially when they
keep beating like there is such a
satisfaction so these cells are the
therapeutic targets of our study so what
we want to do is try to prevent the cell
death of these cells during a heart
attack and on the other hand we try to
regrow we want to push the heart to
actually regenerate and make many more
of these cells so just think about this
though the heart is not made only of
cardiac muscle cells there are another
number of cells also the blood vessels
or the immune system of the nervous
system and then we discovered a more
rare population which has some kind of
cool features let me tell you about this
these cells first of all we can isolate
them from the heart it means we can take
them out of the heart and put them in a
dish not only man we can grow a lot of
this cell
we can use some offensive robotics so we
can go in every day and feed the cells
we go in the weekend we treat them like
our babies and what we were able to do
is to deposit one single cell in a dish
and then grow many of them this is their
special features not all cells can grow
from one this cells means they are
clonal genic and that is why we can call
them cardiac stem cells now we have to
do a lot of experiments then to
understand what these cells really are
for in among these experiments we need
to analyze gene expression now who knows
what is she talking about
what is gene expression well let’s do
one step back I’m sure you have heard
about DNA DNA is a book of instructions
that you receive at Birth from your
mother and your father so each cell of
your body that is will develop in utero
and then will be a readout but it
contains the same book of instructions
so how do you get a clever neuron in the
brain or a clever cadet muscle cells
they keep meeting it’s because these
cells make some specialized sets of
proteins that allow the cell to become
what they have to do so how do we go
from DNA to this special set of proteins
well within the cells there is the cells
can synthesize messenger rna’s there are
specialized molecules they tell the cell
what they have to become if what they
need to make so when we analyze sorry
when we analyze gene expression we
analyze the expression of messenger
rna’s now let’s pretend we’re doing an
experiment here and let’s imagine a each
one of you is a cell and I want to
understand what is the gene expression
in the gene expression let’s pretend
it’s your hair color so what I can do is
take all of your hair pile them up at
the back of the room and then look what
color we can see might see some blacks
and browns some more very blonde I won’t
see the pink here are the fashionistas
sitting on the second floor
second row sorry and even if I see some
blonde
I won’t be able to know who they
belonged to now we’re using new
technologies that allow us to look at
the gene expression in each single cell
this has been a complete change and it’s
going to change biology the way we
understand things let me show you how we
do an experiment so we start from a
piece of heart we chop it up basically
then it goes into a tube you got all the
loose cells and then we run them into a
special machine and in the end we get a
graph you see all these dots here each
dot is a cell then we tell the Machine
okay put one cell in a little well of
this plastic dish and then now we are
able with this technology to study the
expression of about 100 genes in 100
single cells so in a chip which is the
size of your cell phone we can run
10,000 experiments the output is this
this is not grandma’s tablecloth it’s a
he map it’s called and it’s full of data
each of these squares represent the
expression of a gene in a single cell
let’s call him up because when it’s
ready means high expression when it’s
blue means lowest pressure each column
tells you the set of genes that are
expressed in a single cell now by
studying these patterns we are able to
can you predict and start to hypothesize
what a certain cell type could do so we
started to think that the cells were
isolated they grow from one cell maybe
they can become cardiomyocytes so
there’s an image of the cardiac stem
cells in a dish
we took some know dangerous viruses to
make the cells orange and be able to
track them when we sucked them into the
heart then we look three months later
and what happens look how these
beautiful cardiac muscle cells we have
generated so they convince themselves
have become cardiac muscle cells it was
a great result they were done another
experi say well let’s see how the heart
is functioning after we sup in the
cardiac stem cells we do an MRI and the
heart receives themselves is beating
much better but it was something they
did
because they tell you limitation that we
have in the field when use up cells into
the heart the heart is pumping in the
cells wash out so they don’t stay there
for like all three months but after
three months you just have a few tenths
of cells so we have made just a few
cardiac muscle cells covere muscle cells
as if are as thin as a hair so really if
you have made 1020 new cells that cannot
explain what the heart is beating better
so we had to come up with another
hypothesis what we thought is that when
you inject cells into the heart
this might release some factors the
beneficial to the rest of the cells to
the other cells of the heart so first of
all we tested the effect on the cardiac
muscle cells mmm of course we have to
come up with an experiment look at those
beautiful cells that we can use these
are human heart muscle cells in a dish
okay we design an experiment to check
monitor the health of the cells so the
blue cells are healthy cells when they
become red it means that they are dead
the ones you see now are all healthy and
happy then we are the layer of
complication to the experiment actually
we physically add on a second floor to
the plastic dish and on the top floor we
plate cardiac stem cells and as a
control of course we have a dish without
the stem cells then we create a heart
attack in a dish and what happens is
that where we have Cardiacs themselves
we have basically abolished all the
cardiac muscle cell death this is a
great discovery so now what we know is
the Catholics themselves have produced
this magic soup that protects the muscle
cells from dying but how do we go from
that this soup how can we use it
therapeutic lis well we want to
understand what are the critical factors
that mediate this protective effect so
we go back to the single cell gene
expression data and experiments that I
showed you before now this is not a
mistake that is so small
it’s the grandmom’s tablecloths that I
showed before and it’s so small because
now we are using cutting-edge
technologies to look at thousands of
gene expression in thousands of cells so
now we’ve got a new tablecloth for
Grandma with a much higher resolution
and we host a mountain of data so we’re
basically gone from a cell in a haystack
we found this rare cell that Arabic RDX
themselves and now we found a new
University in each of these single cells
and of course then like what do we do
now
it’s a bit overwhelming honestly we’ve
got all this data and now well now we
need to work very closely between
bioinformatician computational
biologists that will use machine
learning will use data mining and then
we need to go back to the bench so we’ll
have to go back and forward a few times
until we have identified the critical
novel factors towards building a new
heart thank you [Applause]
a question to the audience what do you
think is the first cause of death in the
world well I hope you’re not thinking to
cancel that your reading at this light
because in fact it’s ischemic heart
disease its chemical diseases you’re
normally defined as a heart attack it’s
a first cause of death for men and women
and this hasn’t changed for the last 25
years
despite reduction of risk factors I’m
not telling you to start smoking stop
exercising and an LC diet in fact the
reason for this high frequency is the
aging of the population in the more rich
countries and in the poorer countries
people are moving to the cities changing
lifestyle and that brings in more cases
and more heart attacks let’s make sure
that you know what happens during a
heart attack
during a heart attack there is a sudden
loss of the blood flow to an area of the
heart muscles so what happens is you
have a big patch a injured part where
the cardiac muscle cells die now these
days were quite lucky because there are
a number of therapies to counteract and
save our lives
we got clot-busting drugs we got
interventional cardiologists that can
put in a stent into your blood vessels
and restore the blood flow so now 70% of
patients that have a heart attack will
survive however there are a 20 25 % of
people that will develop heart failure
now what is our failure heart failure is
a condition when the heart can not pump
any more efficiently the blood so you
get less blood to your brain to your
muscles you get tired you can think well
and so on the disease is quite serious
it cost a lot of money cost over 100
billion dollars per year globally and
what happens is when you get to the
later stage of the disease the only cure
is heart transplantation this is
obviously not for everyone now why do we
get heart failure well one of the
reasons is that we are not this little
cube monster we’re not axolotls so if
you cut the limb of this little monster
it would regrow if you cut his heart it
will regrow similar happens in the
zebrafish and somewhat surprisingly even
in the heart of neonatal mice just in
the few days of life though what happens
in the human heart well the human heart
is a bit more lazy a little bit more
boring just yet think of this when you
have a scratch in your hand
how long does it take for this king to
regrow and Bri he’ll just a matter of
days well the heart in the heart only
less than 1% to the cardiac muscle cells
regenerate in a whole year so the heart
is very lazy as I said and I mentioned
cardiac muscle cells look at it’s
beautiful organ this is a heart and it’s
made of many or these functional units
that are called cardiac muscle cells or
cardiomyocytes look how beautiful they
are every time I look down a microscope
I get so excited especially when they
keep beating like there is such a
satisfaction so these cells are the
therapeutic targets of our study so what
we want to do is try to prevent the cell
death of these cells during a heart
attack and on the other hand we try to
regrow we want to push the heart to
actually regenerate and make many more
of these cells so just think about this
though the heart is not made only of
cardiac muscle cells there are another
number of cells also the blood vessels
or the immune system of the nervous
system and then we discovered a more
rare population which has some kind of
cool features let me tell you about this
these cells first of all we can isolate
them from the heart it means we can take
them out of the heart and put them in a
dish not only man we can grow a lot of
this cell
we can use some offensive robotics so we
can go in every day and feed the cells
we go in the weekend we treat them like
our babies and what we were able to do
is to deposit one single cell in a dish
and then grow many of them this is their
special features not all cells can grow
from one this cells means they are
clonal genic and that is why we can call
them cardiac stem cells now we have to
do a lot of experiments then to
understand what these cells really are
for in among these experiments we need
to analyze gene expression now who knows
what is she talking about
what is gene expression well let’s do
one step back I’m sure you have heard
about DNA DNA is a book of instructions
that you receive at Birth from your
mother and your father so each cell of
your body that is will develop in utero
and then will be a readout but it
contains the same book of instructions
so how do you get a clever neuron in the
brain or a clever cadet muscle cells
they keep meeting it’s because these
cells make some specialized sets of
proteins that allow the cell to become
what they have to do so how do we go
from DNA to this special set of proteins
well within the cells there is the cells
can synthesize messenger rna’s there are
specialized molecules they tell the cell
what they have to become if what they
need to make so when we analyze sorry
when we analyze gene expression we
analyze the expression of messenger
rna’s now let’s pretend we’re doing an
experiment here and let’s imagine a each
one of you is a cell and I want to
understand what is the gene expression
in the gene expression let’s pretend
it’s your hair color so what I can do is
take all of your hair pile them up at
the back of the room and then look what
color we can see might see some blacks
and browns some more very blonde I won’t
see the pink here are the fashionistas
sitting on the second floor
second row sorry and even if I see some
blonde
I won’t be able to know who they
belonged to now we’re using new
technologies that allow us to look at
the gene expression in each single cell
this has been a complete change and it’s
going to change biology the way we
understand things let me show you how we
do an experiment so we start from a
piece of heart we chop it up basically
then it goes into a tube you got all the
loose cells and then we run them into a
special machine and in the end we get a
graph you see all these dots here each
dot is a cell then we tell the Machine
okay put one cell in a little well of
this plastic dish and then now we are
able with this technology to study the
expression of about 100 genes in 100
single cells so in a chip which is the
size of your cell phone we can run
10,000 experiments the output is this
this is not grandma’s tablecloth it’s a
he map it’s called and it’s full of data
each of these squares represent the
expression of a gene in a single cell
let’s call him up because when it’s
ready means high expression when it’s
blue means lowest pressure each column
tells you the set of genes that are
expressed in a single cell now by
studying these patterns we are able to
can you predict and start to hypothesize
what a certain cell type could do so we
started to think that the cells were
isolated they grow from one cell maybe
they can become cardiomyocytes so
there’s an image of the cardiac stem
cells in a dish
we took some know dangerous viruses to
make the cells orange and be able to
track them when we sucked them into the
heart then we look three months later
and what happens look how these
beautiful cardiac muscle cells we have
generated so they convince themselves
have become cardiac muscle cells it was
a great result they were done another
experi say well let’s see how the heart
is functioning after we sup in the
cardiac stem cells we do an MRI and the
heart receives themselves is beating
much better but it was something they
did
because they tell you limitation that we
have in the field when use up cells into
the heart the heart is pumping in the
cells wash out so they don’t stay there
for like all three months but after
three months you just have a few tenths
of cells so we have made just a few
cardiac muscle cells covere muscle cells
as if are as thin as a hair so really if
you have made 1020 new cells that cannot
explain what the heart is beating better
so we had to come up with another
hypothesis what we thought is that when
you inject cells into the heart
this might release some factors the
beneficial to the rest of the cells to
the other cells of the heart so first of
all we tested the effect on the cardiac
muscle cells mmm of course we have to
come up with an experiment look at those
beautiful cells that we can use these
are human heart muscle cells in a dish
okay we design an experiment to check
monitor the health of the cells so the
blue cells are healthy cells when they
become red it means that they are dead
the ones you see now are all healthy and
happy then we are the layer of
complication to the experiment actually
we physically add on a second floor to
the plastic dish and on the top floor we
plate cardiac stem cells and as a
control of course we have a dish without
the stem cells then we create a heart
attack in a dish and what happens is
that where we have Cardiacs themselves
we have basically abolished all the
cardiac muscle cell death this is a
great discovery so now what we know is
the Catholics themselves have produced
this magic soup that protects the muscle
cells from dying but how do we go from
that this soup how can we use it
therapeutic lis well we want to
understand what are the critical factors
that mediate this protective effect so
we go back to the single cell gene
expression data and experiments that I
showed you before now this is not a
mistake that is so small
it’s the grandmom’s tablecloths that I
showed before and it’s so small because
now we are using cutting-edge
technologies to look at thousands of
gene expression in thousands of cells so
now we’ve got a new tablecloth for
Grandma with a much higher resolution
and we host a mountain of data so we’re
basically gone from a cell in a haystack
we found this rare cell that Arabic RDX
themselves and now we found a new
University in each of these single cells
and of course then like what do we do
now
it’s a bit overwhelming honestly we’ve
got all this data and now well now we
need to work very closely between
bioinformatician computational
biologists that will use machine
learning will use data mining and then
we need to go back to the bench so we’ll
have to go back and forward a few times
until we have identified the critical
novel factors towards building a new
heart thank you [Applause]
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