I'm Malcolm Moore.
And I'm a professor of
cell biology at Memorial
Center in New York.
And I would like to talk to you
today about hematopoietic stem
cells and progenitor cells and their
role in normal blood formation.
What are stem cells?
Well, the simple definition is cells
that replicate and self-regenerate.
This is called self-renewal.
And they can do so extensively, only
limited by a progressive shortening
of the ends of the chromosomes.
This is called telomeric shorting.
And when they lose a
sufficient amount of DNA
at the ends of these
undergo death by a
DNA damage response.
So this is called
the Hayflick limit.
The shortening of
telomeres can be prevented
by telomerase enzyme expression.
And many stem cells, there are different types,
actually produce telomerase.
Embryonic stem cells, those that are
identified as capable of generating
And they give rise to all the
specialized tissues of the body.
Symmetric self-renewal is
basically where the stem cell
gives rise to two
daughter stem cells.
Somatic stem cells, that is to say stem cells of the adult,
include hematopoietic stem
cells, a rare sub-population
of tissue-specific, relatively
that undergo asymmetric division.
They're capable of extensive self-renewal.
And they can give rise not only to
the different types of blood cell,
the red cells, platelets, and white blood cells,
but also the cells of the immune
system and other sub-populations,
such as dendritic cells.
This definition was established
for a hematopoietic stem cells
45 years ago and is
still valid today.
As I mentioned, stem
cells in the bone marrow
are a rare population of cells, only
about 0.01% to 0.001% of all cells.
And as shown in this model,
we can see that in the adult,
symmetric division means
that basically stem cells
replace themselves at each division.
This is a value of 0.5, which
would be the method of determining
whether or not the stem cell was,
on average, totally asymmetric.
But clearly, in the embryo, stem
cells must expand to match growth.
And in umbilical cord blood,
that is the blood that we find
in the cord at the time of birth,
is a very rich source of stem cells
and is used for many
studies on hematopoiesis
stem cell function.
And these represent cells
that were actually derived
from the fetal liver and
they're in the process
of moving to the bone marrow.
And they have the ability not
only to self-renew, but to expand.
That means they undergo
some symmetric divisions.
And on average, this
probability of symmetric
versus asymmetric division
is around 0.6 to 0.65.
And they have these properties for,
in humans, some months after birth,
and some weeks after
birth in the mouse.
We can recognize this sub-population
of feta-neonatal stem cells because
of the expression of the gene SOX17.
Another important point, which we
will discuss in great detail later,
is the importance of the niche
or micro-environment in the bone
marrow, which is critical
as a supportive structure
for maintaining the stem cells
in their undifferentiated state.
Now, this model is a model that
demonstrates the differentiation
of the stem cells, the hierarchy,
if you will, between the most
primitive type of
hematopoietic stem cell,
which is termed the long-term reconstituting hematopoietic stem cell.
It's called a long-term because
if you transplant the stem cells,
in a mouse, for
example, one stem cell
or a few stem cells will persist
throughout the life of the animal,
giving rise to all of the
cells of the peripheral blood
and the immune system.
There is a short-term or even
an intermediate-term stem
cell that have been identified.
And they simply have
shorter durations of ability
to self-renew and
generate the mature cells.
And then we have multipotential
These can give rise also to all
the different types of blood cells.
But they do not self-renew.
So they're basically
a transit population
or a progenitor
population to distinguish
them from the stem cell population.
And as we further progress
we get more specialization and we
recognize what are termed Common
CMPs, that give rise then
to megakaryocytes erythroid
progenitors, which then give
rise to erythrocytes and platelets.
Or the common myeloid
progenitor gives rise to GMPs,
granulocyte monocyte progenitors,
giving rise to neutrophils
and macrophages and also
a type of dendritic cell.
The common lymphoid progenitor
from the multipotential progenitor
gives rise, in turn, to T cells,
B lymphocytes, and natural killer
cell components of the
immune system and also
to a type of dendritic cell.
This is called the
Weissman model because it
has been mostly proposed
by Dr. Weissman.
But it is not necessarily
the final word.