Haematopoiesis Overview

Haematopoiesis

• Haematopoiesis is the formation and development process of blood cells.
• Blood is a highly regenerative tissue, with approximately one trillion cells arising daily in adult human bone marrow.
• Haematopoiesis is a complex process, but it is one of the most understood developmental systems.
• In 1909, Alexander Maximow postulated that blood is organized as a cellular hierarchy, with a single cell at its apex resembling a lymphocyte.
• Four decades later, the hypothesis was proven through functional rescue experiments where the haematopoietic system was reconstructed in irradiated mice via transplantation of cells from healthy donors.

Types of Haematopoiesis

• Embryonic haematopoiesis is the initial blood cell production.
• It occurs in the yolk sac, generating various blood cells like primitive erythrocytes, and some myeloid cells.
• The main function is to facilitate oxygenation of the growing embryo.

Adult Haematopoiesis

• Bone marrow (BM) is the main site of haematopoiesis in adults.
• It provides an environment for the maintenance and differentiation of haematopoietic stem cells (HSCs).
• However, some blood cells mature in other locations, like T and B cells in the thymus and spleen, respectively.
• Modern techniques like cell surface antibodies and multicolour flow cytometry highlight the developmental hierarchy system in haematopoiesis, with HSCs at the top and differentiated cells at the bottom.

Stem and Progenitor Cells

• Haematopoiesis begins with a haematopoietic stem cell (HSC).
• HSCs are rare, approximately 1 in every 20 million nucleated cells in bone marrow.
• HSCs have the ability for long-term self-renewal and differentiate into various cell types.
• Functionally, HSCs can reconstitute a bone marrow that has been destroyed by lethal irradiation or chemotherapy.
• HSCs are not morphologically distinguishable but are identified based on their phenotype using surface markers.

Progenitor Cells

• Committed haematopoietic progenitors are derived from HSCs.
• Progenitor cells become more restricted in their differentiation and proliferation capabilities.
• In vitro culture techniques demonstrate the existence of progenitor cells.

Types of Formed Elements

• Blood sample consists of plasma and formed elements. - Formed elements include platelets (0.1%) and white blood cells (99.9%). - White blood cells consist of neutrophils (50-70%), eosinophils (2-4%), basophils (<1%), lymphocytes (20-30%), monocytes (2-8%). - Red blood cells contribute to 99.9% of the sample.

Sites of Haematopoiesis

• Throughout the prenatal stages, haematopoiesis starts in different parts of the body.
  • Yolk sac: predominant source during early stages of development
    • Liver: plays an important role
    • Spleen: participates in haematopoietic function
    • Bone marrow: the main site for haematopoiesis in adults.

Regulation of Haematopoiesis

• Growth factors, transcription factors, and adhesion molecules are crucial in regulating haematopoiesis.
• Glycoprotein hormones regulate blood cell proliferation and differentiation.
• Stromal cells are a source of growth factors like erythropoietin (Kidney) and thrombopoietin (liver), playing a role in regulating the function of mature blood cells.
• Growth factors regulate different stages of haematopoiesis.

Transcription Factors

• Transcription factors are proteins that bind to specific DNA sequences, regulating gene expression.
• Essential for blood cell development.
• Mutation, deletion, or translocation of transcription factors can lead to haematological malignancies.

Adhesion Molecules

• These glycoprotein molecules mediate cell-cell and cell-matrix interactions.
• Three families exist: Immunoglobulin superfamily, selectins, and integrins.
• They play important roles in various haematopoietic processes.

Summary

• Haematopoiesis is the formation of blood cells. It has two major types, embryonic and adult.
• The process is organized hierarchically, beginning with HSCs and progressing through progenitor cells.
• This process is carefully controlled by numerous factors, including growth factors, transcription factors, and adhesion molecules.