Hematopoeisis

Assessment hematopeoitic stem cell

What is hematopoeisis? development of cells of blood system i.e.	erythrocytes WBCs Platelets

Stroma that supports blood development

Self-renewal, commitment to differentiate

first 8 weeks ells arise in the embryonic yolk sac-primitive system

adult system begins in liver, spleen in late fetus, bone marrow becomes site of development

Details: cell numbers maintained in fairly narrow range in body body likes to see similar circulating numbers respond to injury, blood loss, infection

HSC small population proliferate

What causes a HSC to differentiate? > GSCF, Epo
 * balance of transcription factors,
 * Presence of growth factors

HSC-->Common Lymphoycte Precursor, Commmon MYeloid Precursor division absolute? argued

CMP... gives rise to granulocyte/monocyte and Erythroid/megakaryocyte progenitors
 * Granulocyte precuror gives rise to neutrophils, eosinophils, basophils

Transplantation model Can determine developmental potential of given population of blood cells Cell culture techniques

BFU-burst forming unmits
 * Proliferate
 * Not able ot establish all cel lineages
 * pluripotential
 * granulocytes, megakaryocytes, erythrocytes

CFU >* more restricted than BFU
 * later than burst forming unit
 * can repopulate some cell lineages

Erythoropoeiesis Development of RBCs Maintain a constant mass of RBCs Major component: Hemoglobin morphologic characterization of different stages of RBC developmentis tightly coupled to HB synthesis

HSC->CMP(Need IL-3)->BFU-E(need GM-CSF; proliferative potential)-> CFU-E->

(epo required)

Proerythroblast ->basophilic erythroblast ->polychromatiophilic erythroblast ->orthochromatophilic erythroblast ->reticulocyte->RBC

blue tinge is from ribosomal activity

Megakaryopoeisis HSC->CMP(IL-3)->(BFU(MK)GM-CSF needed->->CFU-MK need thromboboietin (or IL11)

Monopoeiesis and granulopoiesis

Derived from a common progeniotr cell cells of the monocyte series differentiate into tissue macrophages granulopoisis inovlves generation of cells that hae prominent grnaules: neutrophils, eosinophilsk basophils more known about neutrophils b/c more common! basophils, eosinophils chare a common precuror mast cells have basophilic granules are derived from the HSC and develop in tissue

Monocyte and netro[phil development

HSC->CMP->GM-CSF CFU-GM CFU- Monoblast Promonocyte Monocyte

CFU-G MYelopblast Promyeolocyte Myelocyte Metamyelocyte Band Mature Neutrophil

from common progenitor may be cross over iswht some monocytes takes place outside of bone marrow
 * myphopoeisis**

can't tell T vs B lymphocyte under microscope can't be distinguished by eyeball genetically heterogenous functionally surface sturctures life span lymphoid organ to which it homes ID by antibody

HSC, IL-7 Common lympocyte precursor Pro-B Pre-B B cell maturation Immunoglobulin expression IL2,4,5 need to be around

differentiation into plasma cell w/ antibody secretion IL-6, IL-4, IL-10

T-cell development HSC CLP
 * CONCEPT WANT TO WALK AWAY WITH**
 * have common lymphocyte precursor
 * going to be thymus
 * moves through thymus in directional manner
 * one side to other
 * as moves through, acquires cellsurface markers that determine as cytotoxic or helper T cell

Goals of the ourse: undersatnd ways in which HSC precurors are assessed Location of hematopoeisis during embrogeneis and in the adult