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HemeOnc
Hematpoiesis
18
Aerospace Engineering
Pre-School
01/05/2011

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Term
Primitive Hematopoiesis
Definition
Transient, primitive program
Begins in early embryogenesis
First 8 weeks: cells arise in the embryonic yolk sac
Term
Definitive Hematopoiesis
Definition
What we see in the adult
Begins during fetal life in association with vascular structures (fetal aorta, placenta)
Expands in the fetal liver and spleen
In the late fetus the bone marrow becomes the main site of hematopoiesis
Term
Shifting Sites of Human Hematopoiesis
Definition
yolk sac until 3 mos, then liver/spleen peak at 5 months, BM/axial skeleton and lesser degree distal long bones peak at 8-9 mos and decrease.
Term
How do we detect HSCs?
Definition
numbers are low, can’t be detected through microscopy, ID relies on cell surface markers, specifically CD34, in addition to Thy-1la and c-Kit
Term
Where are HSCs from?
Definition
from aorto-gonadic mesonephric region (AGM) in the ventral aspect of the dorsal aorta => hemangioblast => hematopoietic stem cells
Term
Stem Cell differentiate how?
Definition
• Transcription Factors – balance of various TFs predisposes stem cells to differentiate in various ways
• Growth Factors – from bone marrow environment, interact with cells at different stages to promote cell growth
o Early development – cells stay near cytokine-rich bony spicules, receive many growth factors
o Late development – cells migrate into sinuses, become mature & ready for use
Term
What do HSCs diffx into?
Definition
o Common Lymphoid Precursor (CLP) – makes B & T lymphocytes, NK cells
o Common Myeloid Precursor (CMP) – makes various myeloid precursors:
 Granulocyte precursor – gives rise to neutrophils, eosinophils, basophils
 Monocyte precursor – can mature into macrophages
 Erythroid/megakaryocyte precursors – mature into RBCs, platelets
Term
Hemoglobin req what for synthesis
Definition
major protein component of RBCs, requiring globins, protoporphyrin, & iron for synthesis
Term
Process of E-poiesis
Definition
• Process: HSCCMPBFUCFU Proerythroblast  basophilic  polychrom  ortho  retic  RBC
o Proerythoblast – small amount of hemoglobin in RBC
o Basophilic erythroblast – more condensed chromatin, more hemoglobin
o Polychromatophilic erythroblast – maximum hemoglobin produced, nucleus condenses
o Orthochromatophlic erythroblast – nucleus fully condensed
o Reticulocyte – nucleus of RBC is extruded, some RNA remains
o RBC –
Term
what signals BFU/CFU differentiation
Definition
• GM-CSF – granulocyte-macrophage colony stimulating factor, cytokine for BFU/CFU diff
Term
Hgb formation as age progresses (1-2 fetal mo, 2-10 fetal mo, newborn/adult)
Definition
• ζ,ε – hemoglobin heterodimer present in early embryogenesis (1-2 months)
• α,γ – fetal hemoglobin present in later fetal development (2-10 months)
• α,β – adult hemoglobin (newborn onwards)
Term
What's unique about platelet generation?
Definition
Endomitosis – nucleus divides, but cell doesn’t; leads to single polypoid nucleus, hi cytoplasmic volume
Platelet formation – mature megakaryocyte sheds off platelets without nuclei
Term
Key trigger to shed platelets into bloodstream?
Definition
• Thrombopoietin (TPO), IL-11 – play important role in megakaryocyte development – shed platelets into bloodstream
Term
G-CSF is key cytokine to trigger what cell diffx?
Definition
PMNs, o Basophils & eosinophils – have common precursor cell before undergoing final commitment
o Mast cells – similar to basophils, derived from HSC developing in tissue
Term
Lymphopoeisis location of maturation
Definition
o T-lymphocytes – takes place in thymus
o B-lymphocytes, NK Cells – takes place in bone marrow, then secondary lymph tissue (nodes, spleen)
Term
process of b-cell development
Definition
HSC=>CLP=>Pro/Pre-B => mature B-cell => activation, plasma cell
Term
t-cell development
Definition
HSC=>CLP=>thymus, differentiate into αβ, γδ lineages *gamma into periphery…*
Term
interleukins key in t-cell development
Definition
IL-7 important early, later IL-1, IL-2, IL-4
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