haemopoiesis Flashcards
Where does haemopoeisis begin ?
embryonic yolk sac (primitive haemopoisis)
Aortic Gonado Mesonephros (definitive haemopoesis)
why is the Vitelline artery the specific site for formation of blood cells
it has the highest sensitivity for hypoxia & can sense the need for new RBCs
when does haemopoiesis begin ?
3rd & 4th week of embryonic life
Haemopoeitic sites and their timelines
1) Yolk sac (3rd week - 6th week)
2) liver & spleen (6/8thweek to 6/7th month of fetal life)
3) bone marrow (6/7th month to 14 months EUL)
What is Extramedullary haemopoiesis?
Abnormal production of blood by the liver in adult life, usually occurs in disease states
What is a stem cell ?
any cell that has the ability to differentiate and self renew. moves to sites based on demand
What is the cluster of differentiation in a normal stem cell?
CD34+, CD38- , CD33- , THY1+, C-kit+
What are hemangioblasts ?
multipotent cells that give rise to haemopoetic & endothelial cells
What is homing ?
this is the movement of stem cells from the peripheral blood to the bone marrow.
it is regulated by transcription factors.
Growth Factor responsible for homing ?
Stromal-Derived Factor 1 (SDF-1)
*binds to CXCR4 receptors on the surface of stem cells
what is mobilization?
movement of stem cells from the bone marrow to the peripheral blood
growth factors responsible for mobilization ?
1) granulocyte monocyte colony stimulations factor (GMCSF)
2) granulocyte colony stimulating factor (GCSF)
What is HIME?
Haemopoietic Inductive Microenvironment - an envt that is conducive & allows adaptability, survival & proliferation of stem cells
What do cells are contained in the stroma ?
1) adipocytes
2) fibroblasts
3) mesenchymal stem cells
4) endothelial cells
5) macrophages
6) collagen
7)osteoblasts
what are the growth factors secreted by the stroma ?
Interleukin 5, 13, 3
eotaxin
what are growth factors ?
these are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells
*may act locally (SCF) or circulate in plasma (GCSF)
characteristics of growth factors
1) glycoproteins
2) synergic in action
3) act on specific receptors
4) work in hierarchy
5) anti-apoptotic
6) pro-proliferative
7) some are positive in action while some are negative in action
how many percent of erythropoietin is synthesized in the kidney ?
90%
*thrombopoietin is made largely in the liver
how many percent of erythropoietin is synthesized in the kidney ?
90%
*thrombopoietin is made largely in the liver
_ are a major source of growth factors
Stromal cells
Growth factors with positive action include (promote proliferation)
1) IL-3
2) transforming growth factor alpha
growth factors with negative action
1) transforming growth factor beta
2) interferon gamma
*used as a treatment for hepatitis
*contraindicated in pregnant women(can lead to bone marrow suppression)
where is interleukin 3’s activity?
on the lymphoid/myeloid & megakaryocyte/erythrocyte progenitors
__ & __ enhance neutrophil, macrophage/monocyte production?
granulocyte monocyte colony stimulating factor (GMCSF) & granulocyte colony stimulating factor (GCSF)
__ & _ family of transcription factors commit cells to the myeloid lineage
PU1 & CEBP(CCAAT Enhancer Binding Proteins) family
__ & _ family of transcription factors commit cells to the myeloid lineage
PU1 & CEBP(CCAAT Enhancer Binding Proteins) family
What transcription factors play important roles in erythropoietic & megakaryocytic differentiation?
GATA 1, GATA 2 & FOG1
What transcription factors play important roles in erythropoietic & megakaryocytic differentiation?
GATA 1, GATA 2 & FOG1
Two phases of the cell cycle
1) Mitotic(M) phase - here the cell physically divides
2) interphase (I) phase - here chromosomes are duplicated & cell growth occurs prior to differentiation
Two stages of mitotic phase
1) mitosis - nuclear division is accomplished
2) cytokinesis - cell fission occurs
The stages of interphase in cell cycle
1) G1 phase - cell begins to commit to replication
2) S phase - DNA content doubles & chromosomes replicate
3) G2 phase - cell organelles are copied & cytoplasmic content is increased.
What major classes of molecules control the checkpoints of the cell cycle ?
1) cyclin dependent protein kinases
2) cyclins
Define Epigenetics
This refers to changes in DNA & chromatin that affect DNA expression other than those that affect DNA sequence.
characteristics of apoptosis
1) cell shrinkage
2) condensation of nuclear chromatin
3) fragmentation of the nucleus
4) cleavage of DNA at internucleosomal sites
What protease action results in apoptosis
Caspases
