Haematopoiesis Overview and Types

Haematopoiesis Overview

• Haematopoiesis is the formation and development of blood cells.
• Blood is a highly regenerative tissue, with roughly one trillion cells arising daily in adult bone marrow.
• The blood system is a well-understood developmental system, despite its complexity.
• In 1909, Alexander Maximow proposed blood is organized in a hierarchical manner, starting with a single lymphocyte-like cell.
• This hypothesis was proven through functional rescue experiments, demonstrating complete hematopoietic system reconstitution in irradiated mice following transplantation with healthy donor cells.

Types of Haematopoiesis

• Embryonic Haematopoiesis: The initial blood cell production occurs in the yolk sac.
  • It produces transitory hematopoietic cells, including primitive erythrocytes and some myeloid cells.
  • Its main function is to support oxygenation of the developing embryo.
• Adult Haematopoiesis: Bone marrow (BM) is the primary site for adult hematopoiesis, providing an environment for supporting the maintenance and differentiation of hematopoietic stem cells (HSCs).
  • While BM is the main site, some blood cells mature elsewhere, such as T and B cells in the thymus and spleen, respectively.
  • Current analysis using cell surface antibodies and flow cytometry has shown a developmental hierarchy with HSCs at the top and differentiated cells at the bottom.

Stem and Progenitor Cells

• Haematopoietic Stem Cells (HSCs): The starting point of hematopoiesis, characterized by:
  • Long-term self-renewal.
  • Differentiation into diverse blood cell types.
  • Rare cells, approximately one in 20 million nucleated cells in bone marrow (<0.5%).
  • Can reconstitute entire bone marrow from lethally irradiated or chemically treated tissue.
  • Morphologically indiscernible.
  • Phenotypically, human HSCs are CD34+ CD38– and negative for lineage markers (Lin–).
• Progenitor Cells: Derived from HSCs, they have:
  • progressively restricted differentiation and proliferation capacity.
  • demonstrated by in vitro culture techniques.

Composition of Whole Blood

• Whole blood comprises plasma (46-63%) and formed elements (37-54%).
• Formed elements include platelets (0.1%), white blood cells (99.9%).
• White blood cell types include neutrophils (50-70%), eosinophils (2-4%), basophils (<1%), lymphocytes (20-30%), and monocytes (2-8%).

Plasma Composition

• Plasma Proteins: Major components:
  • Albumins (60%): Osmotic pressure regulation, lipid and hormone transport.
  • Globulins (35%): Transport of ions, hormones, lipids, and immune function.
  • Fibrinogen (4%): Essential for blood clotting.
• Other solutes: Include water (92%), electrolytes, organic nutrients, and organic wastes.

Buffy Coat

• Buffy coat is the thin layer between plasma and red blood cell layers containing thrombocytes and white blood cells (0.1%).

Regulation of Hematopoiesis

• Growth Factors: Crucial glycoprotein hormones regulating proliferation and differentiation.
  • Examples include erythropoietin (kidney) and thrombopoietin (liver).
• Transcription Factors: These proteins bind DNA, influencing gene transcription.
  • Mutations in transcription factors can lead to hematological malignancies.
• Stromal Cells: Crucial source of growth factors essential to hematopoiesis; such as those found in bone marrow, for example

Sites of Haematopoiesis

• Haematopoiesis sites shift throughout development.
• Prenatal: Yolk sac, liver, spleen, and bone marrow.
• Postnatal: Primarily bone marrow, with contributions from other sites like ribs, vertebral and pelvic bones, and less prominently lymph nodes and the spleen.