Lecture 16 Hematopoiesis Flashcards
What is a multipotent stem cell?
Multipotent cells give rise to different cell types of a given lineage (adult stem cells).
What is a pluripotent stem cell?
Pluripotent cells give rise to all cells of the embryo and subsequently adult tissues (embryonic stem cell).
What is a totipotent stem cell?
totipotent cells give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development).
Example: a zygote is totipotent
Which type of stem cell gives rise to all cells of an organism?
Totipotent Stem Cell
What type of stem cell gives rise to all cells of the embryo and subsequently adult tissues?
Pluripotent Stem Cells (Embryonic Stem Cells)
What type of stem cell gives rise to different ceel types of a given lineage?
Multipotent Stem Cell (Adult Stem Cell)
True or False:
Embryonic Stem Cells are derived from the inner-cell mass of the blastocyst.
True - embryonic stem cells are derived from the inner-cell mass of the blastocyst.
Can embryonic stem cells be induced from adult tissues?
Yes
Where can adult stem cells be harvested from within the body?
Adult stem cells are harvested from mature organs/tissues (bone marrow).
How many different cell-types must a cell be able to differentiate into to be classified as a stem cell?
At least 2
During what weeks of gestation are nucleated erythrocytes given rise to?
From 2-8 weeks of gestation.
During weeks 2-8 of gestation, where are islands of hematopoiesis (blood islands) found?
In the yolk sac wall.
True or False:
Leukocytes form during weeks 2-8 of gestation.
False - NO leukocytes form during weeks 2-8 of gestation.
In what organ does hematopoiesis first occur during weeks 8-28 of gestation?
Hematopoiesis first occur in the liver and then the spleen during 8-28 weeks of gestation.
When does hematopoiesis in the spleen typically cease?
normally ceases around the time of birth.
At how many months of gestation does hematopoiesis begin to occur in the red bone marrow?
6 months gestation to birth and beyond.
True or False:
Red Marrow is the source of all blood cells?
True
Identify a few of the 6 bones that are responsible for blood cell production in red bone marrow prior to puberty.
- skull
- ribs
- sternum
- vertebrae
- clavicles
- pelvis
- long bones
**After Puberty it is the same except for the long bones.
At puberty most red bone marrow is converted to yellow marrow, but where in the body is red bone marrow usually restricted to for hematopoiesis to continue occurring?
Sternum and Iliac Crests
What is the function of the stroma in bone marrow?
The stroma synthesizes and secretes hematopoietic growth factors.
What kind of cells are found in the stroma of bone marrow?
- Fibroblasts
- Reticular Cells
- Adipose Cells
- Endothelial Cells
What does the parenchyma of bone marrow consists of?
Parenchyma consists of various lineages of hematopoietic cells in different stages of differentiation.
What is the main function of the sinusoids in bone marrow?
Sinusoids in the bone marrow provide access for mature blood cells to move into the circulation.
*Sinusoids are endothelial-lined spaces that connect arterial and venous vessels.
What is a sinusoid?
Sinusoids are endothelial-lined spaces that connect arterial and venous vessels.
What makes up hematopoietic cords and where are they found within the bone marrow?
Hematopoietic cords are bands of parenchyma and stroma lying between the sinusoids.
What percentage of cells are synthesized via granulocytopoiesis?
60% of hematopoietic cells are through granulocytopoiesis.
Fill in the Blank:
Erythrocytopoiesis synthesizes___________percent of erythrocytes.
30%
What percentage of hematopoietic cells are produced through thrombocytopoiesis, monocytopoiesis, or lymphocytopoiesis?
10%
A patient presents to you in clinic with a persistent headache, post-bath pruritus, bone and join pain (specifically in the hip and rib area), and just all around fatigue. Up on receiving their blood work back you notice their ratio for total volume of cells in granulocytopoiesis to total volume of cells in erythrocytopoiesis is 1:5. You know right away what’s wrong with the patient and you diagnose them with what condition?
Polycythemia
What is the normal myeloid/erythroid total volume ratio?
3:1
What is the typical myeloid/erythroid total volume ratio in a patient that has been diagnosed with chronic myelogenous leukemia?
8:1
Which two multipotential stem cells are derived from a hematopoietic stem cell?
1) Myeloid Stem Cell
2) Lymphoid Stem Cell
Which two precursor cells types are derived from lymphoid stem cells? Also, where are each precursor found within the body?
1) T-cell precursor -> in the thymus
2) B-cell precursor -> in the bone marrow
True or False:
The plasma cell is derived from a B-cell in the thymus.
False - the plasma cell is derived from a B-cell in the bone marrow.
Natural killer cells are derived from what precursor?
T-cell precursor in the thymus.
The metamyelocyte is a maturing cell in the lineage that comes from a basophil CFU, which in turn is derived from a myeloid stem cell. What two cells can be derived from a metamyelocyte?
Basophil and Mast Cell precursor
Which CFU committed precursor is a neutrophil derived from?
Granulocyte CFU
The macrophage is derived from a monocyte, but from which committed precursor is a monocyte derived from?
Macrophage CFU
What are the only two cell types that are derived from myeloid stem cells that don’t become mature until they migrate into the peripheral tissue?
Macrophage and Mast Cell
How do mature blood cells get from the hematopoietic cord into the sinusoid? Also, what is this process called and can megakaryocytes do this too?
Mature blood cells migrate from the hematopoietic cords through the sinusoidal endothelial walls into the sinusoids.
This is called: Transendothelial Migration
NO - megakaryocytes (site of platelet production) are too large to translocate and must remain in the stroma.
Are hematopoietic stem cells pluripotential or multipotential?
Pluripotential - are committed to either mydloid or lymphoid stem cell lines.
Myeloid stem cells give rise to all blood cell lines except what?
Lymphocytes
Can hematopoietic stem cells be identified by morphology under the microscope?
NO - cannot be identified by morphology, but can be recognized by cell surface markers.
Which 3 cell types are classified as granulocytes?
1) neutrophils
2) basophils
3) eosinophils
Which 2 cell types are classified as Agranulocytes?
Monocytes and Lymphocytes
What are the two different classifications for leukocytes?
Granulocytes or Agranulocytes
What are the five kinds of colony-forming units that are derived from a myeloid stem cell?
Erythroid CFU
Basophil CFU
Eosinophil CFU
Megakaryocyte CFU
Granulocyte-Macrophage CFU
Which 3 CFUs derived from the myeloid stem cell give rise to white blood cells?
Basophil CFU
Eosinophil CFU
Granulocyte-Macrophage CFU
In which organ is erythropoietin produced?
Kidneys
What triggers the erythroid CFU to differentiate into a proerythroblast?
erythropoietin
What signals a megakaryocyte to differentiate into a megakaryocytoblast?
thrombopoietin
What cell type does erythropoietin act on?
Signals for erythroid CFU to differentiate into a proerythroblast.
Thrombopoietin triggers the differentiation of what cell?
Megakaryocyte into a megakaryocytoblast.
What signals differentiation of basophil CFU to a myeloblast cell?
SFC (stem cell factor or c-kit ligand) and GM-CSF
SFC and GM-CSF signals differentiation of what cell type to turn into a myeloblast?
Basophil CFU
What stimulates eosinophil CFU to differentiate into a myeloblast?
GM-CSF
G-CSF signals a granulocyte-macrophage to differentiate into what type of cell?
Neutrophil
A monoblast is derived from what type of CFU, in which is stimulated by M-CSF to differentiate into a monoblast?
Granulocyte-macrophage CFU
True or False:
Macrophage are not found in the blood.
TRUE
The monoblast and promonocyte are found where in the body?
Still in the bone marrow.
Where would a monocyte be found?
Circulating in the blood (non-functional)
What is the only cell that can still divide in the monoblast to macrophage, Granulocyte-macrophage CFU series?
monoblast can still divide, the others cannot.
Which three cell types in the myeloblast to neutrophil granulocyte-macrophage CFU series have mitotic activity?
1) myeloblast
2) promyelocyte
3) myelocyte
In the myeloblast to neutrophil series, which cell types would you expect to find circulating in the blood?
Band cell and Neutrophil
What is the series from a granulocyte-macrophage CFU to a neutrophil?
GM-CFU –> myeloblast –> promyelocyte –> myeloctye –> metamyelocyte –> band cell –> neutrophil
What is the series from a GM-CFU to a macrophage?
GM-CFU –> monoblast –> promonocyte –> monocyte –> macrophage
What is the fate of a monocyte in the liver?
Kupffer Cell (56%)
What is the fate of a monocyte in the lungs?
Alveolar Macrophage (15%)
What is the fate of a monocyte in bone?
an Osteoclast
What is the fate of a monocyte in the skin?
Langerhans Cell
What is the fate of a monocyte in the brain?
Microglia
What is the fate of a monocyte in the spleen?
Red Pulp
What percentage of monocytes are found in the peritoneum? In other non-specific tissues?
8% in peritoneum
21% in other non-specific tissues.
What is the series of cell differentiation starting with eosinophil and basophil CFUs to either a eosinophil or basophil (or mast cell)?
Eosinophil/Basophil CFU -> myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band cell -> eosinophil or basophil (becomes mast cell from the mast cell precursor in the peripheral tissue).
What is the series when starting with a megakaryocyte CFU and ending with platelets?
Megakaryocyte CFU -> Meegakaryoblast -> Megakaryocyte -> Platelets
What is the cell differentiation series when starting with an erythroid CFU and ending with an erythrocyte?
Erythroid CFU -> Proerythroblast -> Basophilic Erythroblast -> Polychromatophilic Erythroblast -> Orthochromatic Erythroblast -> Reticulocyte -> Erythrocyte
Which cells can divide in the erythrocyte series?
Proerythroblast
Basophilic Erythroblast
Polychromatophilic Erythroblast
Which two cell types in the erythroid CFU to erythrocyte series can be found circulating in the blood stream?
Reticulocyte (can be found in circulation but not always)
Erythrocyte
How long do reticulocytes remain in circulation until they mature into erythrocytes?
1 day
Where is erythropoietin (EPO) produced?
Juxtatubular interstitial cells (renal cortex)
A.K.A. –> the kidneys
What is the target cell for GM-CSF?
Neutrophils Eosinophils basophils monocytes dendritic cells
In what cells are hematopoietic growth factors and cytokines produced?
Endothelial Cells in the Marrow
Fibroblasts
Stromal Cells
Where is granulocyte/monocyte-stimulating factor (GM-CSF) produced?
Endothelial Cells
T-cells
Fibroblasts
Monocytes
What two processes does GM-CSF stimulate?
Granulocytopoiesis and Monocytopoisesis
What is Ameliorates neutropenia associated with?
Chemotherapy or Radiation Therapy
Often patients who are undergoing radiation or chemotherapy present with neutropenia. How can the patients neutrophil level be increased?
A synthetic form of GM-CSF (sargramostim or molgramostim) can be administered to the patient to stimulate more neutrophil production.
What cells produce granulocyte colony stimulating factor (G-CSF)?
Endothelial Cells
Fibroblasts
Macrophages
What is the function of G-CSF?
Directs G-CFU to proliferate and differentiate into myeloblasts.
True or False:
G-CSF can be given to patients following chemotherapy or radiation therapy to treat neutropenia.
True
What does monocyte colony stimulating factor do?
commits GM-CFU to monocytic pathway.
What does erythropoietin do?
Directs E-CFU to proliferate and differentiate into proerythroblasts.
What stimulates the production of erythropoietin in the kidney?
Erythropoietin is produced in the kidney in response to decrease in oxygen saturation.
What is secondary polycythemia and name a few potential causes?
Secondary polycythemia is any abnormal increase in total RBC mass resulting from hypoxia and stimulating release of erythropoietin.
Possible causes include Tetralogy of Fallot and Cigarette Smoke
What is the function of Thrombopoietin?
Directs the formation of megkaryoblasts.
Where is thrombopoietin produced?
Produced in proximal convoluted tubules of the kidney
Is also produced in the parenchymal cells and sinusoidal endothelial cells of the liver
**it has NO therapeutic use.
What are the 4 examples of cytokines that Dr. Anderson presented to use that we have to know?
interleukin-3
GM-CSF
Fit-3 Ligand
Kit Ligand
What do cytokines (primarily interleukins) function to do?
Mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation.
They also engage specific receptors and activate a variety of signaling pathways.
What are the ECM components that function as regulators (hematopoietic growth factors)?
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
Bind to guanine protein-coupled transmembrane receptors
Sdf-1 is an example
