HEMATOPOIESIS.pptxgjhgbhjygvjhhgsgjnvubnl
- 1. HEMATOPOIESIS HAFIZA MASUMA FAHEEM VISITING LECTURER UNIVERSITY OF EDUCATION, LAHORE
- 2. INTRODUCTION Hematopoiesis is the process by which the body produces new blood cells. It occurs in the bone marrow. This complex process involves the differentiation and maturation of hematopoietic stem cells into various specialized cell types, each with its own unique functions. Hematopoiesis plays a crucial role in maintaining our overall health and well-being.
- 4. STAGES OF HEMATOPOIESIS Hematopoiesis, the process of blood cell formation, occurs in different stages during different phases of life. ◦ Embryonic hematopoiesis ◦ Fetal hematopoiesis ◦ Adult hematopoiesis.
- 5. EMBRYONIC HEMATOPOIESIS Embryonic hematopoiesis refers to the formation of blood cells during early embryonic development. It begins around the third week of embryogenesis and occurs in two primary sites: The yolk sac The para-aortic splanchnopleura.
- 6. In the yolk sac, primitive erythrocytes, also known as nucleated erythrocytes, are generated. These cells play a vital role in supplying oxygen to the developing embryo before the establishment of the circulatory system. On the other hand, the para-aortic splanchnopleura produces hematopoietic stem cells (HSCs) and multipotent progenitor cells. These cells give rise to different blood cell lineages, including erythrocytes, granulocytes, monocytes, and lymphocytes. They subsequently colonize other hematopoietic organs, such as the liver and spleen.
- 7. FETAL HEMATOPOIESIS Fetal hematopoiesis begins during the second month of gestation and continues until birth. At this stage, the liver becomes a major site for blood cell production, taking over from the yolk sac and para-aortic splanchnopleura. The fetal liver generates a vast number of erythrocytes, as well as myeloid and lymphoid progenitor cells. It also plays a crucial role in producing hematopoietic stem cells, contributing to the establishment of the definitive hematopoietic system. As gestation progresses, hematopoiesis shifts towards the spleen. This secondary hematopoietic site further supports erythropoiesis and the development of other blood cell lineages.
- 8. ADULT HEMATOPOIESIS Once an individual reaches adulthood, hematopoiesis primarily occurs in the bone marrow. Here, hematopoietic stem cells undergo differentiation and proliferation to maintain a constant supply of mature blood cells. The bone marrow houses distinct microenvironments called niches, which provide the necessary signals and support for the regulation of hematopoietic stem cells. These niches ensure a balance between self-renewal and differentiation, allowing for long-term hematopoiesis. Within the bone marrow, myeloid and lymphoid progenitor cells differentiate into various blood cell lineages, including erythrocytes, platelets, neutrophils, monocytes, eosinophils, basophils, B cells, and T cells.
- 9. HEMATOPOIETIC STEM CELLS Hematopoietic stem cells are vital for hematopoiesis, the process by which blood cells are formed. These versatile cells give rise to all types of blood cells, including red blood cells, white blood cells, and platelets. Hematopoiesis occurs in the bone marrow and is crucial for maintaining a healthy immune system.
- 10. CHARACTERISTICS OF HEMATOPOIETIC STEM CELLS 1. Self-Renewal 2. Multipotency 3. Quiescence 4. Microenvironment Dependence
- 11. ROLE OF HEMATOPOIETIC STEM CELLS IN BLOOD CELL PRODUCTION Upon activation, hematopoietic stem cells can proliferate and differentiate into progenitor cells, which are committed to specific blood cell lineages. These progenitor cells further divide and undergo maturation, ultimately giving rise to the diverse array of blood cells required for proper bodily functions.
- 13. Introduction The process of blood cell formation requires regulation by a specialized microenvironment known as the hematopoietic microenvironment or niche. The microenvironment comprises different types of adherent cells, such as fibroblasts, macrophages, and growth factors. Examples of Hematopoietic Microenvironment Interactions •Leukemia: In leukemic conditions, malignant cells can alter the bone marrow microenvironment, disrupting normal hematopoiesis. For instance, leukemic cells may secrete factors that suppress normal HSC function or alter stromal cell behavior. •Bone Marrow Transplantation: Successful bone marrow transplants require the establishment of a supportive microenvironment for donor HSCs. Conditioning regimens that prepare the recipient’s marrow space and use growth factors post-transplant are essential for engraftment.
- 14. Components of Hematopoietic Microenvironment The components of the hematopoietic microenvironment include bone marrow, cytokines, and growth factors, which interact to support hematopoiesis. 1.Bone marrow stromal cells: Fibroblasts, adipocytes, endothelial cells, and osteoblasts are some of the stromal cells involved in hematopoiesis. These provide structural support and secrete cytokines and growth factors required for hematopoiesis. 2.Growth factors and Cytokines: These include soluble factors like stem cell factor (SCF), interleukins (IL-3, IL-6), and granulocyte colony-stimulating factor (G-CSF). These help the survival, proliferation, and differentiation of HSCs and progenitor cells. 3.Extracellular matrix (ECM): This provides an area for cells to attach and migrate. It comprises proteins like collagen, fibronectin, and laminin. These can bind to the integrins present in hematopoietic stem cells to regulate their behavior.
- 16. Stages of Hematopoiesis (Bone Marrow) There are different stages of hematopoiesis. Hematopoiesis begins with hematopoietic stem cells (HSCs), which either self-renew or differentiate into two different lineages. Once the HSCs choose one lineage, it stays committed and matures into the designated mature blood cells. So, the starting step of hematopoiesis is the self-renewal of HSCs, followed by their differentiation into a particular lineage.
- 17. Self Renewal of Hematopoietic Stem Cells (HSCs) The HSCs have the option to either self-renew or differentiate into mature blood cells. Two contrasting models are proposed to explain this choice. In the stochastic model, the decision is random, while in the instructive model, specific microenvironmental factors and cytokines influence the choice. It’s important to note that these models are not without their controversies, adding to the intrigue of HSC biology. Likewise, there are two types of HSCs: long-term and short-term HSCs. The primary function of long-term HSCs is self-renewal, and short-term HSCs are to differentiate into multipotent progenitors.
- 18. HSCs differentiation and commitment to lineages Short-term HSCs give rise to different lineages and lineage progenitors. These progenitors have two main progenitors: common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs), which produce different blood cells. Upon differentiation, HSCs commit to a specific lineage and mature into respective blood cells. The common myeloid progenitors play a vital role in producing RBCs, platelets, basophils, eosinophils, neutrophils, or macrophages. Similarly, the common lymphoid progenitors contribute to the formation of T, B , or NK (natural killer) cells.
- 19. Maturation and Development of Progenitors Following different processes, the common myeloid and common lymphoid progenitors mature and develop into different blood cells, following different hematopoiesis processes. The diverse processes of hematopoiesis include myelopoiesis, lymphopoiesis, thrombopoiesis, and erythropoiesis, each leading to the production of specific blood cell types. 1.Myelopoiesis forms granulocytes (basophils, eosinophils, or neutrophils) or agranulocytes (macrophages and monocytes). 2.Lymphopoiesis produces T and B lymphocytes. 3.Erythropoiesis forms red blood cells or erythrocytes. 4.Thrombopoiesis forms platelets.
- 21. Intrinsic Regulators 1.Transcription Factors: 1. GATA-1: Essential for erythroid and megakaryocyte differentiation. 2. PU.1: Crucial for myeloid and lymphoid lineage differentiation. 3. RUNX1: It plays a key role in regulating HSCs and developing all hematopoietic lineages. 2.Epigenetic Modifications: 1. DNA Methylation: Regulates gene expression by adding methyl groups to DNA, thereby influencing hematopoietic lineage commitment. 2. Histone Modifications: Acetylation, methylation, and phosphorylation of histones affect chromatin structure and gene expression, impacting hematopoietic differentiation. 3.MicroRNAs: These are small non-coding RNAs that post-transcriptionally regulate gene expression, impacting various aspects of HSC maintenance, self-renewal, and differentiation.
- 22. Extrinsic Regulators 1.Cytokines and Growth Factors: 1. Stem Cell Factor (SCF) binds to the c-Kit receptor on HSCs, promoting their survival and proliferation. 2. Erythropoietin (EPO) stimulates red blood cell production in response to hypoxia. 3. Granulocyte Colony-Stimulating Factor (G-CSF): This promotes the proliferation and differentiation of granulocyte precursors. 4. Thrombopoietin (TPO): Regulates platelet production by stimulating megakaryocyte development. 2.Bone Marrow Microenvironment (Niche): 1. Endosteal Niche: It is rich in osteoblasts, maintains HSC quiescence, and supports self-renewal. 2. Vascular Niche: It comprises endothelial and perivascular cells, facilitating HSC activation and mobilization.
- 24. 3. Cell-Cell Interactions: Direct contact with stromal cells, osteoblasts, and endothelial cells via adhesion molecules (e.g., integrins, cadherins) is crucial for HSC maintenance and regulation. 4.Paracrine and Juxtacrine Signaling: 1. Notch Signaling: Direct cell-cell interactions involving Notch receptors and ligands regulate HSC fate decisions. 2. Wnt Signaling: It is involved in the regulation of HSC self-renewal and differentiation through paracrine mechanisms. 5.Extracellular Matrix (ECM): It provides structural support and presents biochemical signals to HSCs through components like collagen, fibronectin, and laminin.
- 25. Systemic Factors 1.Hormones: ◦ Glucocorticoids: This hormone influence the proliferation and differentiation of specific hematopoietic lineages. ◦ Thyroid Hormones: Affect erythropoiesis and overall hematopoietic activity. 2.Nutritional Status: Adequate levels of vitamins (e.g., B12, folate), iron, and other nutrients are essential for effective hematopoiesis. 3.Immune Signals: Cytokines released during infection or inflammation (e.g., interleukins, interferons) can alter hematopoietic activity to meet increased demand for immune cells.
- 26. Feedback Mechanisms 1.Negative Feedback: 1. EPO Production: It is regulated by oxygen levels; increased red blood cell production reduces hypoxia, decreasing EPO synthesis. 2. Immune Cell Regulation: High levels of mature immune cells can inhibit further production through feedback mechanisms involving cytokines. 2.Homeostatic Balance: Constant monitoring and adjustment of blood cell production ensure that the levels of different blood cell types remain within physiological ranges.