Hematopoiesis

Sruthi Pillai
TSEC
Introduction

primary lymphoid organs - development and
maturation of lymphocytes

secondary lymphoid organs - trap antigen and
interact
Hematopoiesis
Stem cells totipotent, self renewal

Potency totipotent, multipotent/pluripotent, unipotent

All blood cells arise from hematopoietic stem cell
(HSC)

Hematopoiesis - The formation and development of red and
white blood cells

Every functionally specialized, mature blood cell is derived
from the same type of stem cell
Hematopoiesis
Site for hemotopoiesis:
Period of
gestation
Site Role
1
st
week
embryonic yolk
sac
yolk-sac stem cells differentiate into
primitive erythroid cells that contain
embryonic hemoglobin
3
rd
month 7
th

month
fetal liver and
then
to the spleen
major roles in hematopoiesis from the
third to the seventh months of gestation
From 7
th
month
onwards
Bone marrow
major factor in hematopoiesis, and by
birth there is little or no hematopoiesis in
the liver and spleen
Hematopoiesis
Study of hematopoietic stem cells is difficult because:
Scarcity (one HSC per 5 x 10
4
cells in the bone marrow)
hard to grow in vitro

hematopoietic stem cells are maintained at stable levels
throughout adult life self renewal

HSCs enormous proliferative capacity.
E.g. mice hematopoietic system destroyed by X rays will die
within 10 days
Infused with normal bone-marrow cells from a syngeneic mouse
(0.01%0.1% of the normal amount) restores normal
hematopoietic system
Hematopoiesis
Hematopoiesis
Multipotent stem cell HSC differentiates along one of two
pathways:
Lymphoid progenitor cell
Myeloid progenitor cell

In this step, HSC transform into
progenitor cells loose capacity for
self-renewal and are committed
to a particular cell lineage.

Control its differentiation:
Growth factors in its
microenvironment
Hematopoiesis
Lymphoid progenitor
cells give rise to
B cells,
T cells,
NK (natural killer) cells
Dendritic cells

Myeloid stem cells
generate progenitors of
red blood cells
(erythrocytes),
many of the various
white blood cells
(neutrophils,
eosinophils, basophils,
monocytes, mast cells,
dendritic cells),
platelets

Hematopoiesis
Hematopoiesis
In bone marrow - hematopoietic cells grow and mature on a
meshwork of stromal cells (non hematopoietic )

Stromal cells include :
fat cells, endothelial cells, fibroblasts, and macrophages.

Stromal cells provide - hematopoietic-inducing
microenvironment (HIM)

The required growth factors some are water soluble
diffuse through stromal cells reach target

The ones which are not soluble membrane bound
Hematopoiesis Studied In Vitro
Hematopoietic
cytokines required for
proliferation,
differentiation:
1. Colony-
stimulating factors
(CSFs)
2. Erythropoietin
(EPO)

Hematopoiesis Regulated at the Genetic Level
Development of pluripotent hematopoietic stem cells into
different cell types requires expression of different sets of
lineage-determining and lineage-specific genes

For this study: knockout mice a gene has been inactivated
or knocked out by targeted disruption

Knockout technology is one of the most powerful tools
available for determining the roles of particular genes

Many transcription factors that play important roles in
hematopoiesis. E.g. GATA-2, Ikaros
Hematopoietic Homeostasis
Production of mature cells = its loss.
erythrocyte - life span -120 days
Neutrophils - few days
T lymphocytes - 2030 years

To maintain steady-state levels, the average human being
must produce an estimated 3.7 x10
11
white blood cells per day

Steady-state regulation:
Control of the levels and types of cytokines
The production of cytokines with hematopoietic activity by other cell
types, such as activated T cells and macrophages
Removal of some cells by cell death

Programmed Cell Death Homeostatic mechanism