Lec. 2 Hematopoiesis

Exam 1

Define hematopoiesis.

Process of replacing old blood cells

Define differentiation.

Process a cell goes through to become a different type of cell

Define commitment.

When 2 cells from the same precursor cell take different paths to development

What is the precursor to the hematopoietic stem cell (HSC)?

Hemangioblast

What % of HSC’s are in bone marrow? What are they known as due to the fact that they can become any kind of body cell?

0.5%

Known as pluripotent/multipotent cells (PSC/MSC)

What % of bone marrow cells are progenitor cells (PC’s)? What 2 categories can they split into?

• 3%

• Can split into myeloid cells or lymphoid cells

Compared to the HSC’s, when PC’s develop, what is one thing they share with the HSC and one thing they don’t?

Share: unidentifiable morphology

Different: unable to self-renew

What % of bone marrow cells are mature cells?

95%

How can mature cells be identified? What stage does identification start at?

• Identified via morphology (ex. macrophage, neutrophil, etc.)

• Starts at “blast” stage

Most mature cells go through CFU or BFU, then blast, then are finalized cells. What does CFU and BFU stand for? What specific cell has both stages?

CFU: colony forming unit

BFU: burst forming unit

erythrocytes: HSC → CMP → BFU-E → CFU-E → erythrocyte

What are HSC’s capable of? (Hint* 2 things)

1. self-renewal (via daughter cell clones)

2. differentiation into other cells (ex. CMP/CLP)

Why is regulation of HSC into progenitor cells important?

Determines the [blood cells].

The HSC precursor cell (hemangioblast) are governed by cytokines (a type of glycoprotein). What cytokine triggers HSC production into PC’s?

IL-6

HSC’s are not morphologically identifiable. There is also no quantitative assay to measure an amount of them. What type of analysis is used to identify a hemopoietic stem cell?

immunophenotyping via flow cytometry (this checks the antigens of a cell via the device).

Who has more stem cells, an adult or a child?

Child

What are the three stages hematopoiesis will go through during child development? (As in, what three locations do blood cells get produced at and when)

1. Mesoblastic stage (in yolk sac): starts at day 19 of fertilization → week 6/8 of gestation

2. Hepatic stage (liver): week 5 → birth

3. Medullary stage (red bone marrow): Month 6 (first time able to see cells in clavicle) → 5/7 years old

What happens to most red bone marrow after age 5/7? Where does hematopoiesis take place from then on?

• red marrow turns into fat or yellow marrow (no longer produces cells)

• Hemato. takes place in red marrow in flat/irregular bones (skull, vertebrae, ribs)

What cells does bone marrow produce?

ALL cells

What is the pathway that cells take to get out of red bone marrow and into the blood? Give the simplified version and then the slightly more in depth version.

Hematopoietic compartment (bones) moves into the vascular compartment (body)

red marrow (along “cords”) → vascular sinuses (holding area) → blood vessels in bone → peripheral blood

In healthy adults, where are immature blood cells found? What about mature ones?

Immature: red bone marrow

Mature: peripheral blood

Main hematopoiesis takes place in red bone marrow. What are secondary places blood cells can develop (think white)? What are these places called?

• spleen, thymus, lymph nodes

• Extramedullary hematopoiesis

What cells are developed in the thymus?

T cells

The spleen also produces cells (it is extramedullary). What are it’s main functions?

• Culling: destroys damaged/old RBCs

• activates “pitting”: removes/pinches off hazards attached to RBCs and then let’s them through → may result in a spherocyte

• 1st line of defense for blood-borne pathogens

Why does the spleen have red and white pulp? What happens here?

red pulp: erythrocyte inspections (removal of damaged RBCs) / also acts as platelet storage

white pulp: T and B cell production

Lymph nodes are another location for blood cell production (extramedullary hemat.). What cells are produced here and what do the lymph nodes do?

• T and B cells, macrophages

• Fluid from blood enters tissues (lymph) → nodes filter lymph from foreign particles via cells

What can cytokines trigger in a cell?

Inhibit/stimulate…

1. production

2. apoptosis

3. differentiation

4. cell movement (via signaling)

What was the first identified cytokine (growth factor) and what cell type does it affect?

• Colony stimulating (CSF)

• granulocytes

What does the Kit ligand do? (a.k.a stem cell factor (SCF)

stimulates production of HSC and PC’s

How many interleukins (cytokine) are there? What do they do?

• 18

• differentiate WBC’s.