Hematopoiesis

Question 1

What cell marker characterizes the hematopoietic stem cell? Which two lineages can this develop into? Which cells does each lineage make?

Answer 1

• hematopoietic stem cell is CD34+ and becomes myeloid stem cell or lymphoid stem cell
• myeloid: erythroblast (RBCs), myeloblast (granulocytes), monoblast (monocytes), megakaryoblast (platelets)
• lymphoid: B-cells, T-cells, NK cells

Question 2

Where does hematopoiesis occur in utero? What about postnatal?

Answer 2

• 1-2 months in utero: yolk sac
• 2-8 months in utero: liver (also spleen to lesser extent)
• 4 months and on in utero: bone marrow (which is present in ALL bones at this stage)
• postnatal: bone marrow of flat bones (tibia, femur, ribs, sternum) and vertebrae
• (hematopoiesis in tibia and femur drops off around age 20)

Question 3

Which cells secrete EPO? What stimulates EPO production/stimulation? In addition to triggering erythropoiesis, what else does EPO do?

Answer 3

• EPO is released by renal cells in the interstitium outside the tubular basement membrane
• it is released by hypoxic events (specifically by HIF-1, hypoxic-inducing factor 1)
• EPO also down-regulates hepcidin, resulting in an increase in iron absorption needed for erythropoiesis

Question 4

What is the normal reticulocyte count? What do these cells look like on histology? How long do they take to mature to functional RBCs?

Answer 4

• normal RC: 0.5 - 1.5% (OR 20-100 x10^9/L)
• reticulocytes are slightly larger than mature RBCs with a general blue-ish hue; they also have ER remnants that stain dark blue on methylene blue staning
• they mature in 24 hours

Question 5

What does a “left shift” in relation to neutrophils mean? When is it seen? What cell in particular does it refer to?

Answer 5

• a neutrophilic “left shit” means an increase in number of band cells (the direct precursor to neutrophils)
• seen in acute inflammation, etc.
• (band cells have a large horseshoe shaped nucleus; it is not segmented as seen in neutrophils yet)

Question 6

What are the two types of monocytes? What process is each involved in? Which cell markers are used to differentiate between them?

Answer 6

• M1: inflammation; Ly6C positive; converts arginine into NO

- M2: repair; Ly6C negative; converts arginine into ornithine

Question 7

Where is TPO produced? How is it regulated?

Answer 7

• TPO is largely made by hepatocytes (cirrhosis leads to decreased TPO)
• it is made at a constant rate
• it is inactivated when bound to megakaryocytes and platelets (so the more of these, the less TPO is available)
• (each megakaryocyte produces 1000 - 3000 platelets)