Tamira Elul

Fall 2016
Hemopoiesis (also called Hematopoiesis)

Reading:Gartner&Hiatt,AColorTextbookofHistology,3rdedition;Pgs236249.
LectureObjectives
1. Contrast prenatal and postnatal hemopoiesis.
2. Describe the components and histological organization of the bone marrow.
3. Know the concept of the pluripotential hemopoietic stem cell (PHSC), and its two
daughter cells CFU-GEMM (CFU-S) and CFU-L.
4. Understand the factors that regulate erythropoiesis, and the different cells in the
erythropoietic lineage. Identify orthrochromatophilic erythroblasts and reticulocytes.
5. Know the three lineages of granulocytopoesis, beginning from CFU-Eo (of the
eosinophil lineage), CFU-Ba (of the basophil lineage), and CFU-G (of the neutrophil
lineage). Understand at which cell stage these three lineages become visually
distinguishable.
6. Define the stages in lymphopoesis (CFU-Ly, CFU-LyB, CFU-LyT).
7. Describe the formation of platelets from CFU-GEMM, CFU-Meg and
Megakaryocytes.

I. Introduction
Hemopoiesis is the development of different blood cells from precursor cells. It is
a process that involves cell-cell signaling, cell division and cell differentiation. Some of
the molecular signals involved include the interleukins (IL), Granulocyte signaling factor,
macrophage inhibitory protein and erythropoietin.
II. Prenatal and Postnatal Hemopoiesis
Prenatally, hemopoiesis or blood cell formation begins two weeks after
conception, and is subdivided into several phases- mesoblastic, hepatic, splenic, and
myeloid. The first stage involves mesenchymal cells aggregating into blood islands. The
next two stages involve further blood cell formation in the liver and spleen. The last
phase- the myeloid phase involves the formation of blood cells in the bone marrow- a
process which continues post-natally for the rest of life. Blood cells are short lived, and
thus new blood cells are continually being formed.
Postnatal hemopoiesis occurs exclusively in the bone marrow. The bone marrow
is a gelatinous cavity with vasculature that includes arteries, veins and capillaries called
sinuses. Surrounding the sinuses cords of cells are found. These cords of cells are in the
hemopoietic lineage. Another major cell type found in the bone marrow is adipose tissue.
In fact, bone marrow that is not active in hemopoiesis will contain an abundance of
adipose cells, and thus be called yellow marrow.

Tamira Elul
Fall 2016

III. Pluripotential Hemopoietic Stem Cell

Hemopoiesis is based on the theory that all types of blood cells derive from a
common precursor cell- called the pluripotential hemopoietic stem cell (PHSC). This
stem cell divides and gives rise to more stem cells as well as to more differentiated and
restricted stem cells in the hemopoietic lineage. The PHSC is identified by expression of
the marker CD34 on its surface. The PHSC can differentiate into two more restricted
stem cells called colony forming units. The two stem cells are thus CFU-GEMM (also
called CFU-S or colony forming unit spleen). CFU-GEMM will give rise to
granulocytes, erythrocytes, monocytes and megakaryocytes, and CFU-Ly (will give rise
to lymphocytes).
IV. Hemopoiesis
We will focus first on the formation of erythrocytes. In the formation of
erythrocytes, CFU-GEMM gives rise to BFU-E (burst forming unit erythrocyte) and
CFU-E (colony forming unit-erythrocytes). Differentiation of CFU-GEMM into BFU-E
is regulated by the cytokines IL-3, IL-9, steel factor and granulocyte-monocyte
stimulating factor (GMSF) as well as erythropoietin. CFU-E, stimulated by
erythropoietin, will differentiate into a proerythroblast, the first morphologically
distinguishable erythrocyte precursor. Proerythroblasts differentiate into basophilic,
polychromatophilic and orthochromatophilic erythroblasts. The nucleus becomes
noticeably smaller and eccentrically located in the orthrochromatophilic erythroblast.
Also, orthochromatophilic erythroblasts cannot divide. Orthochromatophilic
erythroblasts will differentiate into reticulocytes, which lack a nucleus. When
reticulocytes accumulate enough hemoglobin they are called erythrocytes and released
into circulation. After 120 days or so, red blood cells will display specific antigens on
their surface that will signal for them to be sent to and destroyed in the spleen.
Granulocytopoiesis involves the differentiation of each of the granulocytes. Each
of these three cells derives from its own unipotential (or bipotential) stem cells, which is
a descendent of the pluripotential stem cell CFU-GEMM. The three lineages follow a
similar pattern, and thus are usually considered together. CFU-GEMM will give rise to
CFU-Eo (of the eosinophil lineage), CFU-Ba (of the basophil lineage) and CFU-GM (of
both the neutrophil and monocyte lineages). Each of these stem cells differentiates into
the myeloblasts of its lineage, which divide and give rise to promyelocytes, and then to
myelocytes. Only at the myelocyte stage can specific granules be resolved, and the three
granulocytes differentiated from one another histologically. (Note that CFU-GM
differentiates into CFU-G (which will give rise to myeloblasts of the neutrophil lineage),
and to CFU-M (of the monocyte lineage).
Monocytes derive from CFU-M (which derived from CFU-GM- the bipotential
stem cell that gives rise to both the monocyte and neutrophil lineage). CFU-M are called
monoblasts, and they give rise to promonocytes which will differentiate into monocytes.
Monocytes then differentiate into macrophages when they enter the connective tissue.

Tamira Elul
Fall 2016
CFU-GEMM also gives rise to CFU-Meg the unipotential stem cell of the
megakaryocyte lineage. CFU-Meg will differentiate into megakaryoblasts by a process
called endomitosis (in which the cell replicates its genetic material and cytoplasm, but
does not divide, and the nucleus does not divide as well). Megakaryoblasts are huge cells
with a polyploid nucleus. Megakaryoblasts will differentiate into megakaryocytes, large
cells with a single multi-lobulated nucleus. Megakaryocytes will extend cytoplasmic
processes into sinusoids of the bone marrow and form plasma membrane invaginations
called demarcation channels between these processes. The ctyoplasmic processes will
fragment along the demarcation channels, releasing clusters of proplatelets into the blood
stream. The proplatelets will quickly fragment into platelets in the blood stream.
Lymphopoiesis involves the differentiation of CFU-Ly into two unipotential
progenitor cells- CFU-LyB and CFU-LyT, both of which then go on to become
immunocompetent. CFU-LyB will stay in the bone marrow to become
immunocompetent B lymphocytes, while CFU-LyT will migrate to the thymus to become
completely immunocompetent T lymphocytes. Once B- and T-lymphocytes are
immunocompetent, they will migrate to lymphoid organs such as the spleen and thymus
to form clones.