Lecture 4 - Intro To Hemopoiesis And Stem Cells Flashcards Preview

Block 4 - Heamatology > Lecture 4 - Intro To Hemopoiesis And Stem Cells > Flashcards

Flashcards in Lecture 4 - Intro To Hemopoiesis And Stem Cells Deck (15)
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1

Three stem cell lineage

- Myeloid - give WCC
- Megakaryocyte - give rise to platelet
- erythoiud - give rise to RBC

- cytokines, growth factors, chemokines are responsible for this pathway of differentiation

2

Neutropenia and infection

- severity neutropenia increases the risk of severe infection almost linearly

3

Hemopoietic cell maturation
- stem cell -> progenitor cell -> effector cell

1) proliferative potential
2) lineage commitment
3) maturation induction
4) self renewal

1) proliferative potential decreases over the compartments

2) lineage commitment is non existent in stem cells and then increases as differentiation progresses

3) maturation induction is absent ins tem cell and then increases as differentiation progresses

4) self renewal: only stem cell capable of self renewal and then decreases rapidly as you move down compartments

4

2 features of HSC

- multipotentiality
- self renewal

- hemopoietic reconstituyting ability (wherther it is transplantable or not) determines whether the cell is a stem cell or not

5

HSC vs commited progenitor
- morphology
- responsibveness
- frequency
- cycle
- in vivo markers
- engrafment

- morphology: stem cell smaller
- responsiveness: HSC more
- Frequency: 10-5 vs >10-4
- cycle: GO vs cycling
- in vivo marker: pre-CFU-S vs CFU-S
- engrafment: long term vs early, transitory

6

Lineage restricted stem cells from HSC

- some self renewing cells have a restricted differentiation potential, arising directly from asymmetric divisions of HSC
- normal stem cell self renewal is assymetrical

7

HSC

- ease of collection
- alternative sources available: bone marrow, peripheral blood, cord blood
- utility as gene transfer target
- ability to maintain and manipulate ex vivo
- inexhaustible

8

Induced pluripotent stem cells

- pluripotent stem cells in embryogenesis give rise to HSC
- these cells come back up differentiation tree to give rise to HSC in the bone marrow

9

Hemapoietic cell differentiation and maturation are regulated by cell intrinsic and cell-extrinsic factors

- cell intrinsic: proteins, RNA, micro RNA, lipids, stochastic factors, organelles

- cell extrinsic: hemapoietic growth factors, cytokines, chemokines, small peptides, microvesicles.

10

Regulation of erythoid lineage (RBC)

- via INDIRECT FEEDBACK LOOP
- HSC -> BFU-E -> CFU-E -> erythroblast -> erythrocyte (red cell mass)

- negative feedback loop via O2 sensor -> kidney/Liver -> EPO -> promotes differentiation

11

Human myeloid Colony Stimulating Factors (CSF)

- Multi lineage: IL3, GMCSF

- Lineage restricted:
GCSF - Neutrophil
MCSF - Macrophage
EPO - erythrocyte
TPO - Megakaryocyte

12

Actions of haemoapoietic regulators

- proliferation
- linage commitment
- maturation
- functional stimulation
- promotion of survival
- induction of apoptosis

13

Regulation of Myelopoiesis - WCC

Via DIRECT negative feedback loop

- HSC -> multi-CFC -> GM-CFC -> G-CFC -> mature effector cell

- mature efefctor cell negatively regulate GM/G-CSF (measure WCC mass and promote differentiation)
- inflammation positively GM/G-CSF

14

EPO and TPO

- very similar DNA, escept TP has a very large carboxy terminus

15

The stem cell niche

- cytokines/receptors
- chemolkines/ receptor
- extracellular matrix
- cells
- physical microenvironment: different elasticities in tissues
- blood stem and progenitor cells respond to substrate elasticity