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
1st week embryonic yolk
sac
yolk-sac stem cells differentiate into primitive erythroid cells that contain
embryonic hemoglobin
3rd month – 7th month
fetal liver and then
to the spleen
major roles in hematopoiesis from the third to the seventh months of gestation
From 7th 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 104 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 - 20–30 years
To maintain steady-state levels, the average human being must produce an estimated 3.7 x1011 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