Hematopoiesis - Chp. 4

Hematopoiesis

the process of blood cell production, differentiation, and development

Blood Development Progression:

Stem cell → progenitor → precursor → mature blood cell

Based on developmental potential, what are the three major types of stem cells?

Tooth Plooti Mooti TPM

Totipotential stem cells (Most versatile stem cell)

Pluripotential stem cells (Present several days after fertilization)

Multipotential stem cells (Found in adults)

What are Totipotential stem cells?

Present during the first few hours after fertilization

Can develop into any human cell type

Can support development from an embryo into a fetus

Key distinction: This is the only option in your slides capable of developing into the fetus.

What are Pluripotential stem cells?

Can develop into essentially any cell type

Cannot develop into a fetus

What are Multipotential stem cells?

Derived from pluripotent stem cells

Restricted to a particular family of tissues/cells

Example: Bone marrow stem cells → all types of blood cells

What is the order of stem cell potency hierchy?

Totipotent → Pluripotent → Multipotent → increasingly committed progenitors

Three Phases of Hematopoiesis?

Mesoblastic → Hepatic → Medullary Or: Yolk sac → Liver → Bone marrow

What do Mesoblastic/Yolk Sac/Embryomic Phase do, produce, and the erythrocytes contain?

This is the earliest phase.

• Primitive hematopoiesis occurs in blood islands of the yolk sac

• Begins around day 19 post-conception

• Continues until approximately week 8

Produces:

• Erythrocytes

• Macrophages

• Platelets

The erythrocytes contain:

• Gower hemoglobin

• Portland hemoglobin

What are the Hepatic/Fetal Hepatic Phase timing, development/produce of what, and what organs contribute during this period?

The liver becomes the major site.

Timing:

• Begins approximately 5–7 weeks post-conception

• Continues until approximately 24 weeks / sixth month

• Peak hematopoiesis occurs around 3 months gestation

Developing cells colonizing the fetal liver include:

• Erythroblasts

• Granulocytes

• Monocytes

Eventually, these cells mobilize toward the bone marrow.

The following also contribute during this period:

• Spleen

• Thymus

• Lymph nodes

Exam association: Liver = fetal hepatic phase

What are the Medullary/Myeloid Phase? What is the organ that becomes the major roles and it’s process name? What growth factors are included?

Eventually, bones become large enough to develop marrow cavities.

Around the fifth month, bone marrow takes on its hematopoietic role.

• Bone marrow ultimately becomes the chief organ of definitive hematopoiesis in adults.

• The liver and spleen can serve as supplementary hematopoietic organs when necessary. 

This is called: Extramedullary hematopoiesis

Important growth factors present include:

• EPO

• G-CSF

• GM-CSF

The M:E ratio at this stage is approximately 3:1.

Timeline: Mesoblastic/yolk sac → Hepatic/liver → Medullary/bone marrow

HSC → HSC + differentiating daughter demonstrates what?

Self-renewal through asymmetric division.

Chromatin of an immature blast?

Fine/open.

Chromatin as cells mature?

Condenses/clumps.

Why is immature cytoplasm blue?

Abundant RNA/ribosomes.

Major size exception during maturation?

Megakaryocyte gets larger.

Cytokines: EPO / TPO / G-CSF / GM-CSF / M-CSF / IL-7 targets?

RBC / platelet / neutrophil / Granulocyte + monocyte / lymphoid

Renal failure can cause anemia through what mechanism?

↓ EPO => ↓ eythropoiesis

Mature vs. immature description

Nuclear Changes During Maturation ("The nucleus tells you the cell's age.")

Immature/blast cell

• Fine/open chromatin

• Visible nucleoli

Mature cell

• Condensed/coarse chromatin

• No nucleoli

Why chromatin condensation matters: Open chromatin is generally associated with greater accessibility for transcription.

Therefore: Fine/open chromatin → more transcriptionally active

P___ open more action. p__ closed less action.

As maturation occurs: Chromatin condenses/closed → global transcriptional activity decreases

So if an exam asks what increasingly condensed chromatin indicates: ↓ global transcriptional activity

11. Cytoplasmic Changes

Immature cells

• Deep blue/basophilic cytoplasm

• Abundant RNA/ribosomes

• High N:C ratio

Mature cells

• Less basophilic

• Specialized proteins accumulate

• Granules may appear

• Lower N:C ratio

What does a G-CSF do

G-CSF

Neutrophilic

Stimulates the bone marrow to produce neutrophils (specific WBCs). When it’s too much G-CSF, the bone marrow suddenly floods with neutrophils, and marrow gets crowded. The neutrophils release enzymes that cut the “molecular ropes” holding stem cells inside the marrow, and they drift out to the bloodstream.

Normal myeloid cells but M:E falls to 1:1 why?

Myeloid:Erythroid Ratio — M:E Ratio

Approximately 1:1: Associated with erythroid hyperplasia secondary to severe hemolytic anemia

So: Normal = ~3:1

• Low ratio like 1:1 = relatively more erythroid precursors

• This can occur because anemia/hypoxia stimulates: ↑ EPO → ↑ erythropoiesis → ↓ M:E ratio