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Hematopoiesis

Sites:
1. Yolk Sac (1st few weeks)
2. Liver
3. Bone marrow
a. Vertebral and pelvis
b. Sternum
c. Ribs
d. femur
4. Spleen
5. Lymph nodes

Fetal month 5
- Liver
Age 4
- Long bones become filled with adipose tissue
Age 18
- Mostly hematopoietic tissue is only in the vertebra, sternum, and ribs

Hematopoietic niche
- Sinus endothelial cells
o Cover the inner layer of the venous sinuses
o Controls entry and exit of substances
o Influence osteoprogenitor
- Mesenchymal stem cells
o Skeletal elements
o Adventitial reticular cells
 Covers the wall of the sinuses
o Adipocytes
 Support the differentiation of late stage committed myeloid
o Bone cells
 Form the endosteal lining of bone
o Extracellular matrix
 Proteins with many functions
Stem cells
- Mother cell of all blood elements
- Characteristics
o Multipotent
o Able to replicate
o Apoptosis
- 2 x 10^4 stem cells/human
Myeloid line
- Red cells
- Granulocytes
- Platelets
Lymphoid line
- Lymphocytes

Erythropoiesis
- Burst forming unit (BFU)
o Earliest progenitor committed to erythroid lineage
- Colony forming unit (CFU-E)
o More mature progenitor unit
- Both cannot be identified by conventional light microscopy

Erythropoiesis
- Pronormoblast
o First identifiable by light microscopy
o Large volume
o Has epoietin receptors (EPOR) – “if you give epoetin, cell could divide or
differentiate into division”
- After each cell division
o Volume halves
o More cytoplasmic hemoglobin
- Upon reaching “orthochromic normoblast”
o No further cell division
o Nucleus is extruded
- Reticulocytes
o With remnants of endoplasmic reticulum and ribosomes
- Transcription factors involved in differentiation:
o GATA-1
 Activates erythroid specific genes
o FOG
 Augments or inhibits GATA-1
o SCL
 Essential for maturation of erythroid and megakaryocytic lineage
- Erythropoietin (EPO)
o Principal hormone for regulating erythropoiesis
o Produced principally in the kidney
o May also be produced in the liver
o Gene encoding erythropoietin is activated by a sequence near the 3’ region 
hypoxia sensitive
- Mechanism of Erythropoietin
o Homeostasis is having normal blood oxygen levels
o When will you not have normal oxygen blood levels?
 High altitude
 Smoking
 Asthma
 People who snore
o In hypoxic conditions:
1. Hypoxia signals kidneys to release more erythropoietin
2. Red marrow is stimulated to produce more red blood cells. More red cells
leads to increased oxygen carrying capacity of blood.
3. Homeostasis

Thromboiesis
- Platelets
- Megakaryoblasts
o Lobed nucleus, origin of platelets
o Already express surface adhesion molecules
o Eventually forms demarcation membranes (invaginations of plasma membranes)
o Undergoes endomitosis (nucleus and chromosomes divide inside (Prophase
metaphase, anaphase) but cell membrane doesn’t divide)
o Promoters of megakaryocytic differentiation:
 GATA
 RUNX1
 Thrombopoietin
 Most critical
 Produced in the liver
 Receptor c-mpl
 IL-3, IL-6
 Stem cell factor
 CXCL12
o Whiie mostly confined in the marrow, thrombopoiesis may also occur in the
lungs

Lymphopoiesis
- Develops later, after production of erythrocytes and granulocytes
- (T lymphocytes) after development in the marrow, travels to the thymus for further
development

Myelopoiesis
- Earliest recognizable progenitor: myeloblast
- Commitment to either neutrophilic lineage, eosinophilic lineage, basophilic lineage:
dependent on IL-5 and stem cell factor
- Mitotic ability is lost during the myelocyte stage
- Regulator: colony-stimulating factor (CSF)
o G-CSF
o GM-CSF
o IL-3
o Stem cell factor