36 Questions
What is the role of thrombopoietin-producing osteoblasts in the maintenance of HSCs?
They maintain HSCs in a quiescent state.
What is the function of CXCL12 in the bone marrow niche?
It regulates the migration of HSCs to the vascular niche.
What is the significance of the heterogeneous microenvironment in the bone marrow niche?
It affects HSCs differently depending on location and cell type encountered.
What is the role of endothelial cells in the bone marrow niche?
They form pores that allow HSCs to pass through.
What is the significance of understanding cell-cell interactions in the bone marrow niche?
It is crucial for the development of cell therapies based on HSCs.
What is the likely outcome of the overlap of niches in the bone marrow cavity?
It provides multiple signals simultaneously to HSCs.
During which phase of fetal development does hematopoiesis in the aorta-gonad-mesonephros region disappear?
Hepatic phase
What is the primary site of hematopoiesis during the second trimester of fetal life?
Liver
At what stage of fetal development does the production of megakaryocytes begin?
Hepatic phase
During which phase of fetal development does the spleen contribute solely to lymphopoiesis?
After 1 to 2 weeks of birth
What is the first fully developed organ in the fetus that becomes the major site of T cell production?
Thymus
During which phase of fetal development does hematopoiesis in the bone marrow reach its peak?
Medullary phase
What is the primary site of hematopoiesis in healthy adults?
Bone marrow
When does hematopoiesis in the fetal liver reach its peak?
Third month of fetal development
What is the result of nondevelopment of the thymus during gestation?
Lack of formation of T lymphocytes
What is the term for the ability of HSCs to give rise to all blood cell lineages?
Pluripotency
What is the most widely accepted theory among experimental hematologists regarding the origin of blood cell lineages?
Monophyletic theory
What is the term for the single progenitor stem cell that gives rise to all blood cell lineages?
Hematopoietic stem cell
Why are adults with thymic disturbance not affected?
Because they have maintained a pool of T lymphocytes for life
What is the term for the ability of HSCs to divide and give rise to more HSCs?
Self-renewal
What is the consequence of lack of formation of T lymphocytes in infants?
Uncontrollable infections
What is the characteristic of HSCs that allows them to give rise to multiple cell types?
Pluripotency
What is the primary function of chemokines in the immune system?
To regulate the adaptive and innate immune system
What is the term used to describe the release of HSCs from the bone marrow compartment into the peripheral circulation?
Stem cell mobilization
What is the purpose of targeting the HSC-microenvironment niche interaction in transplantation-based HSC collection?
To cause the release of HSCs from the bone marrow compartment
What is the name of the proteins that are mentioned as complementing cytokine function and helping to regulate the adaptive and innate immune system?
Chemokines
What is the term used to describe the process of harvesting HSCs from the peripheral circulation?
Apheresis
What is the name of the disease that is often associated with the use of recombinant human erythropoietin?
Uremia
What is the primary function of hematopoietic stem cells in a lethally irradiated host?
To reconstitute the hematopoietic system
What is the outcome of the experiment conducted by Till and McCulloch in 1961?
The formation of colonies of HSCs in the spleens of irradiated mice
What is the characteristic of colony-forming units–spleen (CFU-S)?
Ability to self-renew and produce differentiated progeny
What is the role of the common lymphoid progenitor?
To proliferate and differentiate into T, B, and natural killer lymphocyte and dendritic lineages
What is the outcome of the differentiation of the common myeloid progenitor?
The proliferation and differentiation into individual granulocytic, erythrocytic, monocytic, and megakaryocytic lineages
What is the characteristic of undifferentiated HSCs?
Ability to differentiate into lymphoid or myeloid lineages
What is the significance of the experiment conducted by Till and McCulloch in 1961?
It proved the existence of HSCs and their ability to self-renew and produce differentiated progeny
What is the relationship between HSCs and progenitor cells?
HSCs differentiate into progenitor cells committed to either lymphoid or myeloid lineages
Study Notes
Hematopoiesis
- Hematopoiesis in healthy adults is restricted primarily to the bone marrow.
- During fetal development, hematopoiesis occurs in the yolk sac, then in the aorta-gonad-mesonephros (AGM) region, and finally in the fetal liver.
- Hematopoiesis in the fetal liver reaches its peak by the third month of fetal development, then gradually declines after the sixth month, retaining minimal activity until 1 to 2 weeks after birth.
Mesoblastic Phase
- Hematopoiesis is considered to begin around the 19th day of embryonic development after fertilization.
- Cells from the mesoderm migrate to the yolk sac, where some form primitive erythroblasts.
- These cells pass through pores in the endothelial cytoplasm, are released into the vascular sinus, and then move into the peripheral circulation.
Hematopoietic Stem Cells (HSCs)
- HSCs are predominantly quiescent, maintained in a non-dividing state by intimate interactions with thrombopoietin-producing osteoblasts.
- HSCs are capable of self-renewal, are pluripotent, and can give rise to differentiated progeny.
- HSCs can reconstitute the hematopoietic system of a lethally irradiated host.
Stem Cell Theory
- The monophyletic theory is the most widely accepted theory among experimental hematologists, suggesting that all blood cell lineages are derived from a single progenitor stem cell called a pluripotent HSC.
- The polyphyletic theory suggests that each of the blood cell lineages is derived from its own unique stem cell.
HSCs and Cytokines
- HSCs can differentiate into progenitor cells committed to either lymphoid or myeloid lineages.
- The common lymphoid progenitor proliferates and differentiates into T, B, and natural killer lymphocyte and dendritic lineages.
- The common myeloid progenitor proliferates and differentiates into individual granulocytic, erythrocytic, monocytic, and megakaryocytic lineages.
- Cytokines and chemokines complement each other to regulate the adaptive and innate immune system.
Thymus Development
- Non-development of the thymus during gestation results in the lack of formation of T lymphocytes.
- Adults with thymic disturbance are not affected because they have developed and maintained a pool of T lymphocytes for life.
Clinical Applications
- Understanding the relationships between HSCs and their microenvironment is critical to the advancement of cell therapies based on HSCs, such as clinical marrow transplantation.
- A recent chemokine-related discovery has led to a successful transplantation-based HSC collection strategy targeting the HSC-microenvironment niche interaction to cause release of HSCs from the bone marrow compartment into the peripheral circulation.
This quiz covers the process of hematopoiesis during fetal development, including the role of the yolk sac and the aorta-gonad-mesonephros region.
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