Hematology 5: Hematopoiesis

hematopoiesis

is the process of blood cell formation in the bone marrow

what does hemopoiesis maintain

homeostasis by balancing cell proliferation, differentiation and apoptosis

hematopoiesis specifics

The process responsible for the replacement of circulating cells

Depends on the proliferation of precursor cells that still retain mitotic capability

Governed by multiple cytokines

Takes place in a specialized microenvironment

Importance of Hematopoiesis

Blood cells are short-lived and need constant replacement.

The variety of distinct blood cell types ensures proper immune function, oxygen transport, and clotting.

Can rapidly increase production in response to stress (e.g., infection, blood loss).

Hematopoietic Stem Cells (HSCs):

the starting point of all blood cells

Hematopoietic System Overview

HSCs → Progenitor Cells → Maturing Cells → Mature Blood Cells

Differentiation

•The process that generates the diverse cell populations

•The appearance of different properties in cells that were initially equivalent

Commitment

When two cells derived from the same precursor decide to take separate routes of development

Maturation

•The entire process, from commitment to when the cell has all its characteristics

Circulating cells

•Mature cells with limited life span – terminally differentiated

•Incapable of mitosis

lymphocytes are the exception - expand when in contact with antigen

HSC’s

self renewing and multipotent

Multilineage differentiation potential

Quiescent cell population—population size stable – haven’t matured, inactive

Population maintained by self-renewal

Not morphologically recognizable

Measured by functional clonal assays in vivo and in vitro

progenitor cells

limited self renewal, lineage restricted

3% of total hematopoietic precursor cells

Restricted developmental potential (multipotential → unipotential)

Population amplified by proliferation

Transit population without true self-renewal

Not morphologically recognizable, use stain

Measured by clonal assays in vitro

maturing cells

morphologically identifiable, lose proliferative ability

Greater than 95% of total hematopoietic precursor cells

Committed (unipotential) transit population

Population amplified by proliferation

Proliferative sequence complete before full maturation

Morphologically recognizable

Measured by morphologic analysis; cell counting differentials

HSC characteristics

•Multipotential (can form all blood cell types).

•Self-renewal (divide to maintain their population).

•Mostly quiescent (not actively dividing).

•Morphologically indistinguishable (similar to small lymphocytes).

Phenotype of HSCs

Identified using cell surface markers:

•CD34+ (stem cell marker)

•CD90+ (Thy-1)

•CD133+

•Negative for lineage-specific markers (Lin-)

Cannot be recognized by morphology alone—identified using flow cytometry (FACS).

osteoblastic niche in bone marrow

•Supports and maintains quiescent HSCs.

Vascular Niche in bone marrow

Provides signals for activation, proliferation, and differentiation.

What is Differentiation?

Process where stem cells become specialized blood cells

Commitment

The irreversible decision to follow a specific lineage

2 main progenitor pathways

common lymphoid progenitor

common myeloid progenitor

•Common Lymphoid Progenitor (CLP)

•Gives rise to lymphocytes (T, B, NK cells).

•Common Myeloid Progenitor (CMP)

•Gives rise to Myeloid cells (granulocytes, monocytes, RBCs, platelets).

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maturing cells

cells are morphologically recognizable

•Earliest recognizable cell—”Blast”

•Lymphoblast, myeloblast, megakaryoblast

•Measured by nuclear and cytoplasmic characteristics

•Classify the lineage

•Development stage

cytokines regulate hematopoietic cell’s in

survival, proliferation, differentation

growth factors act in ways of

•Paracrine

•Autocrine

•Juxtacrine

Early-acting (Multilineage) Cytokines:

SCF (Stem Cell Factor)

Flt3 Ligand

IL-3, GM-CSF

Lineage-Specific Cytokines:

•EPO (Erythropoietin) – RBC production.

•TPO (Thrombopoietin) – Platelet production.

•G-CSF, M-CSF – Granulocyte and monocyte growth.

Cytokines bind to specific cell surface receptors to activate signaling pathways.

Major receptor types:

Receptor Tyrosine Kinases (RTKs) – direct activation (e.g., SCF, FL).

Cytokine receptor superfamily – require intracellular kinases (e.g., IL-3, IL-5)

Most hematopoietic cytokines signal through JAK-STAT Pathway:

Cytokine binds receptor.

JAK kinases activate STAT transcription factors.

STAT proteins enter nucleus and regulate gene expression.

Hematopoietic Microenvironment

Provides support for blood cell development.

Includes:

Stromal cells (fibroblasts, osteoblasts, adipocytes).

Extracellular matrix (collagen, fibronectin).

Cytokines & adhesion molecules (SDF-1, VCAM-1).