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ANAT390 Lecture 18 Hematopoiesis
Blood cell production
What are the four stages at which hematopoiesis occurs?
2) Early Fetal/Hepatic
4) Late Fetal/Postnatal/Myeloid - in bone marrow, mesodermally derived
Do hematopoetic stem cells ever travel to the liver or spleen?
Yes, under pathologic conditions or under physiological stress
What is a hematocytoblast?
Hematopoietic stem cells
Normally nonproliferative and found in hematopoietic cords, can be induced to proliferate
Which two lineage progenitors can be formed from hematocytoblasts?
Myeloid and lymphoid
How does lineage restriction affect potency and differentiation?
Lineage restriction leads to a decrease in potency and an increase in differentiation
What are venous sinusoids?
Expanded capillaries allowing ease for diffusion even for large cells.
What do hematopoietic cords contain?
HSC's, lineage progenitors, blasts, and RBCs
Supportive stromal cells (fibroblasts modified as reticular cells with long processes that contact many cells)
How is hematopoiesis regulated?
By long range acting endocrine hormones and by short range acting paracrine factors. Paracrine factors may either be secreted into the stromal ECM or remain tethered to the surface of stromal cells
Provide an example of a paracrine factor and an endocrine hormone.
Stem Cell Factor (paracrine) and erythropoietin (endocrine)
How does stem cell factor regulate hematopoiesis?
Stem Cell Factor is a ligand that acts in a paracrine manner
Sets up localized, spatially-defined stem and progenitor cell niches within the bone marrow
SCF is produced by osteoblasts
SCF binds to c-Kit transmembrane receptor on the surface of stem and progenitor cells
What is a hematopoetic synapse?
Areas where the hematopoietic cells and stromal cells are in close contact
Contain multiple short-range factors and ECM factors
Describe the 6 stages in the erythrocyte lineage.
2. Basophilic erythroblast
3. Polychromatophilic erythroblast
4. Orthochromatophilic erythroblast
Which hormone stimulates the erythrocyte lineage?
Produced by kidney epithelial cells
Describe the 5 steps in EPO secretion.
1. The kidneys detect reduced O2-carrying capacity of the blood.
2. When less O2 is delivered to the kidneys, they secrete EPO into the blood.
3. EPO stimulates erythropoiesis in the bone marrow.
4. The additional circulating erythrocytes in the blood increase the O2-carrying capacity of the blood
5. The increased O2 carrying capacity of the blood relieves the initial stimulus that triggered erythropoietin secretion.
Describe EPO receptor signaling.
EPO binds to transmembrane "cytokine receptors" on cells of the Erythroid lineage
Recruits cytoplasmic kinase amplifiers (=JAKs)
Generates phosphorylated messengers which can directly affect transcription (=STATs)
What is the relationship between hematocrit and blood viscosity?
As hematocrit increases, blood viscosity increases.
What are the two components of the circulatory system?
Lympathic system and cardiovascular system
What are the three layers in blood vessels?
1. Tunica intima
2. Tunica media
3. Tunica adventitia