60% of the liver cells are hemopoietic,also liver remains the primary erythropoietin transcription throughout fetal life.
Hormone receptors are the large proteins present in the target organs.Each receptor is highly specific.Cytokines are peptides secreted bycells into the extracellular fluid and can function either as autocrines,paracrine or endocrine hormones
Embryology hemopoiesis final
• Hemopoiesis is a continuous, regulated process of
blood cell production that includes: cell renewal,
proliferation, differentiation and maturity. The
embryo requires red cells for the transport of
maternal oxygen to permit its growth and
• During embryogenesis, hemopoiesis occur in
temporally distinct sites including yolk sac, the
fetal liver and the preterm bone marrow, Hence the
process has been divided intothree(3) main
phases; mesoblastic phase, the hepatic phase and
the medullary phase.
Erythropoiesis is established soon after
implantation of the blastocyst, with
primitive erythroid cells appearing in the
yolk sac blood islands by day 18 of
gestation. In developing embryos, blood
formation occurs in aggregates of blood
cells in the yolk sac called blood islands.
As development progresses,blood
formation occurs in spleen, liver and
When these organs (i.e thymus,liver and
spleen) resume their hemopoietic
funtions,it is refered to as extramedullary
hemopoiesis which may cause the
organs to increase in size substantially.
During fetal development,liver functions
as the main hemopoietic organ since the
bones and bone marrow are yet to
develop and as such the liver is enlarged
o Hematopoiesis generally is considered to begin on
the 19th day of embryologic development, after
o Progenitor cells of mesenchymal origin migrate from
the aorta-gonad-mesonephros region of the
developing aorta-splanchnopleura to the yolk sac.
o The cells arising from the aorta-gonad-mesonephros
region give rise to hematopoietic stem cells [HSC’s],
but not to primitive erythroblasts found in the yolk
sac which arising from mesodermal cells, initially line
the cavity of the yolk sac.
These primitive cells migrate from periphery into the central cavity
of the yolk sac where they develop into primitive erythroblasts.
The remaining cells surrounding the cavity of the yolk sac are
called ANGIOBLASTS and form the future blood vessels.
The yolk sac phase of hemopoiesis is characterised by the
development of primitive erythroblasts that produce measurable
amounts of hemoglobin.
This phase of hemopoiesis occurs intravascularly, or within a
developing blood vessel(that is within the vascular network rather
than in the extracellular space) and does not contribute
significantly to definitive hemopoiesis.Yolk sac erythroblasts remain
nucleated as they circulate. They are characterised by more rapid
maturation,increased sensitivity to erythropoietin and a shortened
life span compared to fetal and adult erythroblasts. They are
extremely large cells (megaloblasts).
The yolk sac erythroblasts have increased sensitivity to
• The liver serves as a primary source of red cells from 9th to
the 24th weeks of gestation and is characterised by
recognizable clusters of developing
erythroblasts,granulocytes and monocytes.
• The developing erythroblast in this phase signal the
beginning of definitive hemopoiesis with a decline in
primitive hemopoiesis of the yolk sac.
• In addition,lymphoid cells begin to appear, in this
phase,hemopoiesis occurs extravascularly.The
hemoglobins present in this phase include; HbF,HbA,HbA2.
• The liver remains the primary site of erythropoietin
transcription throughout life.
The fetal liver contains abundant hematopoietic progenitor
cells including CFU-GEMM(Colony forming units –
granulocyte-erythroid –monocytes-macrophages and CFUGM(Colony forming unit granulocyte-monocyte).
Along with the development of the hemtopoietic system, the
liver acquires the characteristics of the metabolic organ(that
is,it shows an increase in size).
Furthermore, Oncostatin M(OSM),an interleukin -6- family
cytokine,in combination with glucocorticoids induced
maturation of hepatocytes.
NB: Oncostatin M is expressed in the liver and it’s receptor is
expressed predominantly in hepatocytes. This largely
accounts for a transient expansion of the fetal liver during
o On analysis, fetal liver revealed a significant
reduction in hemopoietic stem cell pool,
suggesting the reduction in cellularity
observed postnatally and is due to insufficient
expansion during fetal development.
o Since Beta-catenin correlated with cell
proliferation during prenatal liver development
and regeneration,analysis carried out showed
that total beta-catenin protein levels were low
at birth(postnatal days 0-5),but were induced
at postnatal day 5 and remained elevated until
postnatal day 20 and returning to near adult
levels(old livers) during postnatal days 25-30.
In addition,studies have shown that the
polyubiquitin(Ubc)gene is required for
fetal liver development and it was highly
expressed in hematopoietic cells,hence a
transfer of the hematopoietic process to
the bone marrow may lead to a decrease
or slowing down of the fetal liver
Hemopoietic cells of the fetal liver exist in a
specific microenvironment that controls their
proliferation and differentiation.
This microenvironment is created by different cell
populations, including epitheliocytes,
macrophages various stromal
elements(fibroblasts, myofibroblasts, vascular
smooth muscle and endothelial cells,
mesenchymal stromal cells).
Hemopoietic function of the organ reaches its
peak during the first 2-4 postnatal days.
o It begins in 5th month of development and occurs in
medulla of bone marrow.
o Mesenchymal cells migrate into bone and differentiate into
skeletal and hemopoietic cells.
o Detectable levels of substances such as; EPO,fetal
Hb,adult Hb, etc. occurs in this phase.
o Tissues where lymphoid development occurs are
classified into primary and secondary lymphoid tissues.
The primary includes the bone marrow,thymus and is
where T&B cells are derived.
The secondary includes spleen, lymph nodes,gut
association lymphoid tissue and is where
lymphoid cells become competent.
There are two types of marrow which are,the red
bone marrow and the yellow bone marrow .
The yellow marrow is hemopoietically inactive
and composed of adipocytes while the red are
found in the
In newborns, all marrow is red but most later
REGULATION OF HEMOPOIESIS
o It is regulated by various
combination of various cytokines stimulate the
proliferation and/or differentiation
hemopoietic cell types. Bone marrow stromal cells
are the major source of hemopoietic cytokines in
the non-infectious state. In the presence of infection,
cytokines produced by activated macrophages
induce hemopoietic activity. Some hemopoietic
growth factors such as the Granulocyte –
Macrophage colony stimulating factor are given to
stimulate white blood cell formation in cancer
patients receiving chemotherapy which kills their red
bone marrow cells as well as cancer cells.
Knowledge of the unique characteristics of fetal
hematopoiesis and the changes that occur at and around
birth is a necessary backdrop for understanding the
differences between neonatal and adult blood.
Erythropoietin (EPO ) has a central role in regulating the
rate of proliferation and differentiation of erythroid
precursors, as it is the most important cytokine regulator
of mammalian erythropoiesis. Targeted disruption of EPO
or its receptor leads to almost complete blockage of fetal
liver erythropoiesis, resulting in fetal death.
Trisomy 21 is associated with an increased frequency of
pediatric acute leukemia,especially megakaryoblastic
leukemia and acute lymphoblastic anaemia(ALL)
Trisomy 21 induces perturbation of hematopoiesis in the
human fetal liver. They show 2 types of abnormalities:
1.A bias in hematopoietic stem cells towards the
erythrocyte-megakaryocyte lineages with an increase in
2.Impaired B cell differentiation with a marked
decrease in B cell progenitors.This indicate that trisomy 21
induces multiple distinct defects in fetal hematopoiesis,which
favour the emergence of transient myeloproliferative disorder
and megakaryoblastis as well as B cell leukemia.
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