Lecture 16 Hematopoiesis Flashcards
List the characteristics of Stem Cells
May proliferate extremely well
Self-renewing
May differentiate into several (at least 2) different cell-types
May reconstitute tissues after injury
Define Totipotent Cells
Give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development)
Define Pluripotent Cells
Give rise to all cells of the embryo and subsequently adult tissues (embryonic stem cells
Define Multipotent Cells
Give rise to different cell types of a given lineage (adult stem cells)
Where are embryonic stem cells derived from?
Inner-cell mass of blastocyst
What is the developmental capacity of an embryonic stem cell?
Pluripotent, differentiate to all cell lineages
Where do adult stem cells come from?
Harvested from mature organs/tissues (bone marrow)
What is the developmental capacity of an embryonic stem cell?
Multipotent
Describe the hematopoietic sites during weeks 2-8 of gestation
Islands of hematopoiesis (blood islands) found in yolk sac wall
Give rise to nucleated erythrocytes
No leukocytes form during this phase
Describe the hematopoietic sites during week 8-28 of gestation
Hematopoiesis first occurs in liver and then spleen
Normally ceases around time of birth
Describe hematopoietic sites during six weeks gestation to birth and beyond
Hematopoiesis occurs in red bone marrow
_______ is the source of all blood cells
Red marrow
Prior to puberty, where does red marrow exist?
Skull, ribs, sternum, vertebrae, clavicles, pelvis, long bones
After puberty, where does red marrow exist?
Same as before, except long bones
Describe Extramedullary Hematopoiesis
In certain disease states, blood cell formation may occur in liver and spleen
In time, most marrow is converted to yellow marrow, and red marrow is usually restricted to where?
Sternum and iliac crests
Describe the stroma of bone marrow
Contains fibroblasts, reticular cells, adipose cells, & endothelial cells
Synthesizes & secretes hematopoietic growth factors
Describe the parenchyma of bone marrow
Consists of various lineages of hematopoietic cells in different stages of differentiation
Describe the sinusoids of bone marrow
Endothelial-lined spaces that connect arterial & venous vessels
Provides access for mature blood cells to move into the circulation
Describe the hematopoietic cords of the bone marrow
Bands of parenchyma and stroma lying between the sinusoids
Where the actual blood cell formation is occurring
What is the distribution of hematopoietic cells?
60% in granulocytopoiesis
30% in erythrocytopoiesis
10% in thrombocytopoiesis, monocytopoiesis, and lymphocytopoiesis
Myeloid/erythroid ratio
Total volume of cells in granulocytopoiesis/total volume of cells in erythrocytopoiesis
Name the characteristics of hematopoietic stem cells
Pluripotent
Can self-renew
Produce two kinds of multipotent precursor cells
Cannot be identified by morphology but can be recognized by cell surface markers
What are the two multipotential precursor cells produced by hematopoietic stem cells?
Myeloid stem cells
Lymphoid stem cells
What do myeloid stem cells give rise to?
All blood cell lines except lymphocytes
What do lymphoid stem cells give rise to?
Lymphocytes
What are the five kinds of colony-forming units that myeloid stem cells give rise to?
Erythroid CFU (from myeloid, but prod. RBCs) Megakaryocyte CFU (from myeloid, prod. RBCs) Basophil CFU (white blood cells) Eosinophil CFU (white blood cells) Granulocyte-Macrophage CFU (white BCs)
Lymphoid Stem Cells give rise to what two kinds of cell lines?
T-cell progenitor
B-cel progenitor
Where do T-cell progenitor cells mature?
In the Thymus
Where do B-cell progenitor cells mature?
In the Bone Marrow
List the series for Granulocyte-Macrophage CFU (macrophage series)
Monoblast - can divide
Promonocyte
Monocyte - normally found in circulation
Macrophage
List the series for Granulocyte-Macrophage CFU (neutrophil series)
Myeloblast - can divide Promyelocyte - can divide Myelocyte - can divide Metamyelocyte Band Cell - found in circulation Neutrophil - found in circulation
List the series for Eosinophil and Basophil CFU
Myeloblast - can divide Promyelocyte - can divide Myelocyte - can divide Metamyelocyte Band cell - found in circulation Eosinophil or Basophil (becomes mast cell) - found in circulation
List the series for the Megakaryocyte CFU
Megakaryoblast
Megakaryocyte
Platelets - found in circulation
List the series for Erythroid CFU
Proerythroblast - can divide Basophilic erythroblast - can divide Polychromatophilic erythroblast - can divide Orthochromatic erythroblast Reticulocyte - found in circulation Erythrocyte - found in circulation
What produce hematopoietic growth factors and cytokines?
Endothelial cells in the marrow, fibroblasts, and stromal cells
What are the three major groups of hematopoietic growth factors?
Colony - stimulating factors
Erythropoietin and thrombopoietin
Cytokines (primarily interleukins)
What produces granulocyte/monocyte colony-stimulating factor (GM-CSF)?
Endothelial cells, T cells, fibroblasts, and monocytes
What do GM-CSFs stimulate?
Granulocytopoiesis and Monocytopoiesis
Granulocyte colony stimulating factor directs:
CFU-G to proliferate and differentiate into myeloblasts
What can be used following chemotherapy or radiation therapy to treat neutropenia?
Granulocyte colony stimulating factor (G-CSF)
Monocyte colony stimulating factor commits:
CFU-GM to monocytic pathway
Erythropoietin directs:
CFU-E to proliferate and differentiate into proerythroblasts
Where is erythropoietin produced and in response to what?
Produced in the kidney in response to decrease in oxygen stimulation
What is secondary polycythemia?
Any abnormal increase in total RBC mass resulting from hypoxia and stimulating release of erythropoietin
What are the possible causes of secondary polycythemia?
Tetralogy of fallot and cigarette smoke
Thrombopoietin directs formation of:
Megakaryoblasts
Where is thrombopoietin produced?
In proximal convoluted tubules of kidney
In parenchymal cells & sinusoidal endothelial cells of the liver
What do cytokines do?
Mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation
Examples of Cytokines
Interleukin-3
GM-CSF
Fit-3 ligand
Kit ligand
Name other ECM components that also play a role in hematopoietic growth regulation
Heparin Sulfates
Collagens
Laminin
Fibronectin
What do chemokines do?
Regulate blood cell trafficking and homing to sites of need
May serve as positive and negative growth regulators
What do chemokines bind to?
Guanine protein-coupled transmembrane receptors
Give an example of a chemokine
Sdf-1
