week 8

• DEV2011 Early human development from cells to tissues
• Lecture - Haematopoiesis
• Julia Young, PhD, Department of Anatomy and Developmental Biology, Monash University
• Lecture - major topics

  • Background - what is blood, and what does it do?
  • Foundational information - the origins of the haematopoietic lineages
  • The broader research/clinical context - role of the different blood cells
  • The bigger picture - blood in the adult - normal and pathological contexts

  
• Lecture objectives


  • To understand the role and basic components of blood
  • To know which germ layer gives rise to blood cells
  • To understand the concept of the haemangioblast and blood islands
  • To know the difference between primitive and definitive haemopoiesis
  • To know the sites in the body in which blood cell development occurs

  
• Blood


  A loose connective tissue, constantly circulated around the body by the heart (cardiac muscle!)
• Connective tissue


  Blood is mostly liquid (plasma), with a cellular component - "formed elements" (Erythrocytes, Platelets, Leukocytes)

  
• Blood volume of average adult human is ~5.5 litres
• Blood functions


  • Distribution of O2 to tissues
  • Distribution of CO2 and nitrogenous products, respectively, to the lungs and kidneys
  • Transportation of nutrients
  • Regulation of body temperature, pH, electrolytes, glucose and cholesterol levels
  • Maintenance of vascular fluid volume
  • Protection against infection and prevention of blood loss following injury
• Plasma


  The extracellular matrix of the blood system, makes up around half of the blood content (and is around 90% water), transports nutrients, metabolic residues and hormones
• Plasma components


  • Plasma proteins (7%) - Albumin, Alpha, beta and gamma globulins, Fibrinogen
  • Inorganic salts (0.9%)
  • Amino acids, vitamins, hormones, lipoproteins etc. (2.1%)
• Haematopoiesis (or haemopoiesis/hemopoiesis)


  The generation or formation of blood

  
• Haemopoiesis in vertebrates occurs in two phases: primitive (embryonic) and definitive (adult)
• Development of blood cells

  1. Yolk sac

  2. Liver

  3. Spleen

  4. Bone marrow

  5. Vertebral and pelvis

  6. Sternum

  7. Ribs

  8. Lymph nodes
• Primitive (embryonic) haematopoiesis


  A transient phase that provides the embryo with its first blood cells, occurs in the yolk sac
• Primitive haematopoiesis


  • Provides the embryo with its first blood cells
  • Occurs in the yolk sac
• Early implantation: epiblast and hypoblast

  1. Cells of the inner cell mass become epithelial like, and delaminate to form two layers (bilaminar germ disc)

  2. Upper (dorsal) layer = epiblast

  3. Lower (ventral) layer = hypoblast

  4. Hypoblast forms primitive/parietal (extra-embryonic) endoderm that lines the yolk sac

  5. Hypoblast also gives rise to extra-embryonic (splanchnic mesoderm)
• Yolk sac


  The extraembryonic mesoderm undergoes a separation, then closes to isolate an area of the yolk sac (the secondary yolk sac)
• A section of the yolk sac becomes surrounded by endoderm, and is ultimately incorporated into the embryonic gut
• Blood cells are derived from the lateral plate mesoderm - the splanchnic
• Primitive haematopoiesis


  • All blood cell types except lymphocytes are produced but erythrocytes (red blood cells) predominate
  • Embryonic erythrocytes differ from adult erythrocytes as they are large and nucleated, and express embryonic globin genes

  
• Haemangioblasts


  Blood progenitors that give rise to both blood cells and endothelial cells that line blood vessels

  
• Embryonic circulation


  The intraembryonic vitelline and umbilical vessels link to the yolk sac and the placenta, respectively, allowing primitive erythrocytes to begin to circulate throughout the embryo
• Definitive (adult) haematopoiesis provides the foetus and adult with the various cell types that make up blood and generates haemopoietic stem cells (HSCs) that will last the lifetime of the individual
• Definitive haematopoiesis


  Occurs in the aorta-gonad-mesonephros (AGM) region, ultimately in the liver, placenta, spleen and bone marrow
• Differences between primitive and definitive haematopoiesis

  • Timing of haematopoiesis
  • Sites of blood cell production
  • Morphology of the cells produced
  • Type of globin genes active in red blood cells

  
• Haemopoietic stem cells (HSCs)

  Derived from splanchnic mesoderm surrounding the dorsal aorta, capable of self-renewal and giving rise to all blood cell types
• Production of the haematopoietic system

  1. Pluripotent stem cell

  2. Committed progenitors

  3. Differentiated blood cell
• In adults, all blood cells are derived from stem cells in the bone marrow
• Bone marrow transplantation


  Can restore the patient's entire haematopoietic system following chemotherapy
• Bone marrow


  • A complex, highly cellular tissue that functions in haematopoiesis, phagocytosis of cell debris, storage and recycling of iron, and production of antibodies
• Colony Stimulating Factors (CSFs) drive cell fate choices in the haematopoietic system
• Colony Stimulating Factors (CSFs)

  Cytokines/growth factors made by stromal cells of the bone marrow that stimulate the growth and differentiation of progenitor cells into different blood cell types
• ex


  Highly cellular tissue
• Functions of highly cellular tissue

  • Haematopoiesis
  • Phagocytosis of cell debris
  • Storage and recycling of iron essential for Hb synthesis
  • Production of antibodies
• Bone Marrow

  In adults, is restricted to the medullary cavities of certain bones – vertebrae, ribs, pelvis, cranial bones, proximal ends of femur and humerus
• Blood cell types in the bone marrow


  • (collated image!)
• Colony Stimulating Factors (CSFs)

  The developmental path taken by the descendant of a HSC depends on which cytokines/growth factors it encounters. Many of these cytokines are made by stromal cells of the bone marrow. Colony stimulating factors derive their name from their ability to stimulate the growth and differentiation of progenitor cells into colonies containing different blood cell types in vitro. These colonies are called colony forming units (CFUs). Some CSFs act on one blood cell lineage and others act on multiple lineages.
• A model for the origin of mammalian blood and lymphoid cells

  
• Colony stimulating factors can direct the differentiation of neutrophils and macrophages