Stem Cells & Hematopoiesis

Question 1

What are stem cells?

Answer 1

cells w/ high self-renewal but low mitotic index; undistinguished cell morphology; combinations of surface proteins are stage specific (CD34 (+), HLA-Dr (-))

Question 2

What is a totipotent cell?

Answer 2

unlimited cell potential

Question 3

What is a pluripotent cell?

Answer 3

multi-organ potential

Question 4

What is a progenitor cell?

Answer 4

limited stem potential

Question 5

What is a precursor cell?

Answer 5

cells committed to differentiate

Question 6

What are the sources of stem cells?

Answer 6

1. embryonic (blastocyst, embryonic germ cells)
2. adult tissues (bone marrow, mesenchymal, hepatic, neural)

Question 7

What is the difference between endogenous and induced stem cells?

Answer 7

endogenous stem cells are patient’s own cells that are transfected with transcription factors and are reverse-differentiated into desired cell type

Question 8

How can stem cells be controlled?

Answer 8

• secretion of soluble effector molecules (ILs, cytokines, chemikines, GFs)
• effector molecules bind to cells to direct their differentiation

Question 9

What lineages does the hemocytoblast produce?

Answer 9

• common myeloid progentior: red blood cell, megakaryocytes, & white blood cells (granulocytes, monocytes)
• comon lymphoid progenitor: lymphocytes (Plasma cell, T cells)

Question 10

What is a colony-forming unit?

Answer 10

collection of hematopoietic stem cells; the more mixed, the more potential for different cell types

Question 11

What are the Hematopoietic Growth Factors?

Answer 11

• Multi-potential: early acting factors
• Erythropoietic: EPO
• Granulopoietic: G-CSF, GM-CSF
• Megakaryocytopoietic: TPO
• Lymphopoietic: ILs

Question 12

What is a niche?

Answer 12

extracellular matrix in which stem cell regenerates; ECM can define the cells and how they develop

Question 13

Define the roles of the following ECM components:

• Fibronectin
• Thrombospondin
• Hemonectin
• Heparan sulfate & Chondroitin sulfate

Answer 13

• fibronectin: interact w/ integrins on cell surface
• thrombospondin: binds soluble cytokines to present to cells
• hemonectin: binds myeloid cells
• heparan sulfate & chondroitin sulfate: bind various ligands

Question 14

What do stromal cells do for stem cells?

Answer 14

secrete ECM molecules, present cell surface molecules & GFs

Question 15

What do endothelial cells do for stem cells?

Answer 15

support differentiation, permit targeting and adhesion, permit transmigration of cells

Question 16

What do osteoblasts do for stem cells?

Answer 16

vital for successful ingraftment:

• serete cytokines
• promote engraftment
• CD166 defines both HSC and binding site on OBs

Question 17

Are you suggesting stem cells migrate? Why?

Answer 17

• different sites of hematopoiesis during development
• different bones in body have equivalent levels of activity
• stem cells found in peripheral blood

Question 18

Describe a megakaryocyte.

Answer 18

• large
• polyploid
• found in bone marrow
• gives rise to thrombocytes –> platlets

Question 19

What are the steps in developing thrombocytes?

Answer 19

• CFU-MK-E pluripotent cells
• CFU-MK
• Megakaryoblast endomitosis –> DNA synthesis w/o cell division
• Megakaryocyte
• Platelets

Question 20

How does platelet interact with environment?

Answer 20

responds to changes in cellular environment thru receptors that interact w/ activating soluble molecules:
thrombin, ADP, epinenphrine, serotonin

Question 21

What does the thrombin receptor on the platelet do?

Answer 21

• It is a protease activated receptor (PAR- enzyme!)
• acitvation site for platelet
• has 7 transmembrane loops

Question 22

How do platelets interact w/ filamentous molecules at site of injury?

Answer 22

• interacts with fibrinogen (forms fibrin), collagen, von Willebrand factor
• activates clotting

Question 23

What are the steps of erythroid differentiation?

Answer 23

1. proerythbrolast
   
   • large cell, large nucleus w/ 3 nucleoli, no granules, blue
2. basophilic erythroblast
   
   • slightly smaller, cytoplasm is more blue staining (more RNA)
3. polychromatic erythroblast
   
   • ​less blue staining, nucleus is more condensed
4. orthrochromatophilic erythroblast
   
   • no longer undergo mitosis
5. reticulocyte
6. erythrocyte

Question 24

What are the steps of myeloid differentiation?

Answer 24

1. Myeloblast
   ​​​looks similar to a proerythroblast
2. ​Promyelocyte
   ​​makes granules
3. Early Neutrophilic/ Eosinophilic/ Basophilic Myelocytes​​
4. Late Neutrophilic/ Eosinophilic/ Basophilic Metamyelocyte
   no longer undergoes mitosis
5. Band Cell (neutrophils)/ Eosinophilic Myelocyte
6. Mature Neutrophil/ Eosinophil/ Basophil