OVERVIEW OF HEMATOPOIESIS

hematopoiesis

formation of blood cellular components

embryonic development

hematopoiesis occurs during — and throughout adulthood to produce and replenish the blood system

hematopoietic stem cells (HSCs)

can be used as a model system for understanding tissue stem cells and their role in aging and oncogenesis

erythrocytes

transport oxygen and waste products

leukocytes

`function in an organism’s immunity

platelets

function in blood clotting

stem cells

Cells that are capable of self-renewal and differentiation into multi-lineage cells

Embryonic stem cells (pluripotent)

have the ability to generate all tissues in the body

Tissue-specific stem cells (multipotent)

give rise to mature cells of a particular tissue

surface markers

Several tissue-specific stem cells have been identified and prospectively purified based on their —-

hematopoietic stem cells (HSCs)

the best characterized stem cell population

hematopoietic stem cells (HSCs)

Self-renew and differentiate into committed hematopoietic progenitors

multipotent progenitors (MPPs)

HSCs differentiate into —-

FALSE

TRUE OR FALSE. multipotent progenitors (MPPs) have the capacity to self-renew

lineage-committed progenitors

MPPs can generate —-

Common lymphoid progenitors (CLPs)
Common myeloid progenitors (CMPs)

lineage-committed progenitors

T-lymphocytes, B-lymphocytes, natural killer (NK) cells

CLPs differentiate into

granulocyte/macrophage progenitors (GMPs)
megakaryocyte/erythrocyte progenitors (MEPs)

CMPs give rise to

mature granulocytes, monocytes, macrophages

GMPs differentiate into

Mature granulocytes

Eosinophils, basophils, and neutrophils

Monocyte

A type of WBC that circulate in the blood

Macrophages

Monocytes that have migrated into tissues

platelets and erythrocytes

MEPs differentiate into

CD33, CD11b, CD14

lineage-specific marker of myeloid

CD71, GPA

Erythroid lineage-specific marker

CD41, CD61

megakaryocytic lineage-specific marker

CD10, CD19

B-lymphoid lineage-specific marker

CD3, CD7

T-lymphoid lineage-specific marker

bone marrow

HSCs are mainly contained in the

growth factors
chemotherapeutic agents

HSCs are increased by administering —- and/or some —-, which will allow the use of peripheral blood as well as bone marrow to obtains HSCs for stem cell transplantation

extramedullary hematopoiesis

In some pathologic conditions (hematologic malignancies), —- is observed and HSCs can be found in other tissues including the spleen and the liver

quiescent state

Most of the HSCs remain in a —- (inactive phase) to prevent rapid exhaustion of HSCs

FoxO family transcription factors

protect HSCs from oxidative damage and increase the expression that promote quiescence

ATM

a serine/threonine plays an important role in the maintenance of HSC quiescence

Thrombopoietin/MPL signalling

contribute to the maintenance of HSC quiescence by regulating interaction of HSCs with the osteoblastic niche of the bone marrow

multidrug-resistant (MDR)

HSCs express high levels of —- genes to protect HSCs from stress or genotoxic agents

TRUE

TRUE OR FALSE. Hematopoietic growth factors are a type of cytokine

hematopoietic growth factors

Facilitates the function of mature blood cells

hematopoietic growth factors

Regulates the proliferation, survival, and differentiation of hematopoietic precursor cells

site of their production or circulate in the blood

Hematopoietic growth factors/cytokines act locally near the —-

hematopoietic growth factors

Produced by different types of hematopoietic or non-hematopoietic cells and usually affect more than one lineage

TRUE

TRUE OR FALSE. Purified recombinant cytokines have been generated and utilized experimentally

hematopoietic growth factors

Genes that are associated with —- have been identified, cloned, and sequenced

hematopoietic cell production

Several of hematopoietic growth factors/cytokines/cytokines have been in clinical use to stimulate —-

Erythropoietin (EPO)

critical for the production of erythrocytes (RBC)

Thrombopoietin (TPO)

required for the production of megakaryocytes (platelets)

Chemokines

Important in regulating hematopoietic cell trafficking and homing

Homing

● migration of HSCs to the blood across the endothelial vascular tissue to different organs and to their bone marrow niches
● Requires active navigation; kung saan siya (HSC) dapat mapunta with the guidance of chemokines
● First and essential step in stem cell transplantation

CXCL12 (SDF-1)

expressed in the bone marrow stromal cells and microvascular endothelial cells

CXCR4

expressed by HSCs and the receptor for CXCL12

CXCL12-CXCR4 chemokine signaling

involved in HSC maintenance and engraftment

B and T cell development
Inflammation
Immune surveillance

Other chemokines and their receptors also play roles in

○ Stem Cell factor (SCF)
○ FLT-3 ligand
○ Granulocyte/macrophage colony stimulating factor (GM-CSF)
○ G-CSF
○ M-CSF
○ Interleukins (IL-3 to IL-7, IL-11, Il-13, & IL-15)
○ Interferons

Other important growth factors:

during gastrulation in the extraembryonic yolk sac

when do the first hematopoietic cells arises?

blood islands

where do the first hematopoietic cells arise?

Primitive hematopoiesis (or initial hematopoiesis)

serves a supportive role to rapidly produce erythroid cells, platelets and macrophages prior to the formation of the circulatory system

blastula
mesoderm, ectoderm, and endoderm

During gastrulation, cell movement results in a massive reorganization of the embryo from a simple spherical ball of cell called —- to the three (primary) germ layers——- —in the development of the embryo.

mesenchyme of the yolk sac

Beginning in the first month of prenatal life, primitive hematopoiesis starts outside the embryo in the —- as blood islands

primitive erythroblasts

the mesenchyme of the yolk sac contain predominantly —-

primitive erythroblasts

large and megaloblastic, are formed intravascularly and retain their nuclei

aorta-gonad mesonephros (AGM)

Definitive hematopoiesis in mammals takes place in the —- region of the embryo

placenta, liver, and spleen.

Hematopoietic cells migrate to the —-

liver

At the 6th week, hematopoiesis begins in the —-

liver

major hematopoietic organ of early and middle part of fetal life

Definitive erythroblasts

become non-nucleated red cells are formed extravascularly in the liver (granulopoiesis and megakaryocytes are present to a lesser degree)

Middle part of fetal life

spleen and lymph nodes have minor role in hematopoiesis

Latter half of fetal life

bone marrow becomes an important site of blood cell production

bone marrow

After birth, the —- is the only site for the production of erythrocytes, granulocytes, and platelets

HSCs and committed progenitor cells

— are maintained in the marrow.

Lymphocytes (B cells)

continue to be produced in the marrow, and in the secondary lymphoid organs (e.g. spleen, thymus)

T lymphocytes

matures and differentiates in the thymus and also in the secondary lymphoid organs

active hematopoietic (red) marrow

At birth, the total marrow space is occupied by

increases

As body growth progresses, marrow space

flat bones and the proximal parts

Later in childhood, only the —- of the long bones of the upper and lower limbs are sites of blood cell formation

Thrombopoiesis

Platelet production

reticulocytes

Babies (where more young cells are present) produce more —-

anemia

More reticulocytes (immature blood cells) are produced by the bone marrow of patients with —- to compensate for the condition

Immature

—- blood cells in peripheral smears can indicate the presence of a disease, such as lymphoma or myeloma (cancer)

Myeloblast (Myeloid series)

Seen in peripheral smears