Haemopoiesis
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Haemopoiesis
Maj Gen Dr Muhammad Ayyub
MBBS, PhD (London), MRCPath (London), FRCPath (UK)
Prof & HOD AM College
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Blood cells have limited lifespans, and need to be replaced
with precisely matching numbers -
Young replacing cells come, by many divisions and steps of differentiation, from stem cells
stem
cell
Hematocytopoiesis
HEMATOPOIESIS
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Cell hierarchy (Haemopoiesis schematic representation)
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HEMATOPOIESIS Subdivisions
stem
cell
Myelopoiesis
PMN
Bas
Lym
Mon
Eos
Pla
RBC
Lymphopoiesis
Granulopoiesis
Monocytopoiesis
Erythropoiesis
Megakaryopoiesis Thrombopoiesis
{
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stem
cell
HEMATOPOIESIS Lineages for
GranulocyteLymphocyte
MonocytePlateletsRBC
Lymphopoiesis
Granulopoiesis
Monocytopoiesis
Erythropoiesis
Thrombopoiesis
Lymphoblast Monoblast Myeloblast
Myelocyte
Metamylelocyte
Band granulocyte
Pro-Myelocyte
Reticulocyte
Pro-erythroblast
Basophilic erythroblast
Orthocromatic erythroblast
Polychromatic erythroblast
Megakaryoblast
Megakaryocyte
Pluripotent stem cell (Hemocytoblast)
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Megakaryopoiesis
PMN
Bas
Lym
Mon
Eos
Pla
RBC
Granulopoiesis
Monocytopoiesis
Erythropoiesis
{ Similar precursor produces Mast cells
Monocyte or a related precursor gives rise to many specialized phagocytes & antigen-presenting cells
Macrophages Kupffer cells Langerhans cells Dendritic cells Microglia Osteoclasts etc
FURTHER DIFFERENTIATIONS
Similar precursor produces Natural killer cells
B lymphocytes become Plasma cells
Thrombopoiesis
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Sites of Haemopoiesis
• Yolk sac
• Liver and spleen
• Bone marrow– Gradual replacement of
active (red) marrow by tissue inactive (fatty)
– Expansion can occur during increased need for cell production
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DMM00_B3.ppt
• Axial skeleton
• Inner spongy bone
• Bone marrow is in the holes
• Bone marrow is a highly organized / regulated organ
BLOOD IS MADEIN THE BONE MARROW
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• All blood cells arise from “mother” (stem) cells
– Self renewing
– Safe from harm
– Pluripotent
• Blood production is highly regulated
– Messages from the body (e.g. erythropoietin from kidney)
– Microenvironments produce specific cells
• Cytokines (SCF, IL3)
• Growth factors (G-CSF)
Normal bone marrow
BAS03_20.ppt
BONE MARROW: THE SOURCE OF BLOOD AND OUR
IMMUNE SYSTEM
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SCHEMATIC OF HEMATOPOIESIS
PSC CFU-GEMM
PlateletsMega
Erythrocytes
Pre-B
B Lymphocyte
T Lymphocyte
Grans / Monos
BFU-E CFU-E
RES03_3.ppt
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Introduction
• Limited Life span of :• Granulocytes
• Erythrocytes
• Platelets
• Lymphocytes
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Introduction
• Stem cells• Self renewal• Plasticity
• Progenitor cells• Developmentally-restricted cells
• Mature cells• Mature cell production takes place from the more
developmentally-restricted progenitors
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Stem cells
• Self-renewal• Normally in G0 phase of cell cycle
• The capacity for self-reproduction is vastly in excess of that required to maintain cell production for normal lifetime
• As cells increase in number they differentiate as well
• Multipotentiality• Capacity to generate cells of all the
lymphohaemopoietic lineages
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Progenitor cells
• Encompasses from immediate progeny of stem cells to differentiation cells committed to one lineage
• Progenitor cells become progressively more restricted in their differentiation and proliferation capacity
• Late progenitor cells eventually restricted to one lineage
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Regulation of Haemopoiesis
• There should be a balance between cell production and cell death except at the times of requirement
Controlled cell death
Controlled cell production
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Regulation of Haemopoiesis
Local environmental controlStromal cell mediated Haemopoiesis
Haemopoietic growth factors (Humoral regulation)Apoptosis
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Interaction of stromal cells, growth factors and haemopoietic cells
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Local and Humoral regulation of Haemopoiesis
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Haemopoietic growth factors• GM-CSF
• Granulocyte-Macrophage colony stimulating factor
• M-CSF• Macrophage colony stimulating factor
• Erythropoietin• Erythropoiesis stimulating hormone
(These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation)
• Thrombopoietin• Stimulates megakaryopoiesis
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Haemopoietic growth factors
• Cytokines• IL 1 (Interleukin 1)• IL 3• IL 4• IL 5• IL 6• IL 9• IL 11• TGF-β
• SCF (Stem cell factor, also known as kit-ligand)Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell
proliferation on their own, but are able to synergise with other cytokines to recruit nine cells into proliferation
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Basophil
Eosinophil
RBC
Neutrophil
T Lymphocyte
Monocyte
Platelets
B Lymphocyte
Pluripotent Stem Cell
CommittedStem Cell
CFU-MegMegakaryocyte
Lymphoid Progenitor Cell
CSCPSC
LPC
MPCMyeloid Progenitor Cell
BFU-E
CFU-E Colony-forming
Unit - ErythroidCFU-M Colony-forming
Unit -Monocyte
Colony-forming Unit - Monocyte.Granulocyte
CFU-GM
CFU-G
CFU-Eo
CFU-Mast
HEMATOPOIESIS Early lineages
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Basophil
Eosinophil
RBC
Neutrophil
T Lymphocyte
Monocyte
Platelets
B Lymphocyte
Pluripotent Stem Cell
CommittedStem Cell
CFU-MegMegakaryocyte
Lymphoid Progenitor Cell
CSCPSC
LPC
MPCMyeloid Progenitor Cell
BFU-E
CFU-E
CFU-M
Colony-forming Unit - Monocyte.Granulocyte
CFU-GM
CFU-G
CFU-Eo
CFU-Mast
HEMATOPOIESISGrowth factors
M-CSF
IL-3, GM-CSF*
*
*
G-CSF
IL-6
IL-3
SCF IL-1
**
EPO
TPO
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Erythropoiesis and erythrocytes
• Lifespan – 120 days• Non nucleated• Biconcave disc• Production regulated
by Epo• Needs Fe, B12, folate
& other elements for development
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ERYTHROPOIESIS
In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages and into
less easily detected early stages *
ERYTHROBLAST
basophilicpolychromatophilic
stem
cell
orthochromatophilic
NORMOBLAST
RBC
*
-blast is the common suffix for an immature form of a cell
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ERYTHROPOIESIS
ERYTHROBLAST
basophilicpolychromatophilic
stem
cell
orthochromatophilic
NORMOBLAST
RBC
polychromatophilic because, in the cell, orange-staining hemoglobin is accumulating, while the blue ribosomes necessary for its synthesis are present, but declining
This idea continues in the form of the reticulocyte which is an RBC released to the blood, but still with a network of blue ribosomal material persisting amongst the hemoglobin
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ERYTHROPOIESIS 2
In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages and into less easily detected early stages
stem
cell
ERYTHROBLAST
PSC
CSC
MPC
BFU-E
Pluripotent Stem Cell
Committed Stem Cell
Myeloid Progenitor Cell
Burst-forming Unit - Erythroid
Used for some specialization, but more for massive cell division, as conveyed by “burst”
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