The Initial Stages of Hematopoiesis

HSC Population Maintenance

The hematopoietic stem cell (HSC) population maintains its population through a process called self-renewal. Self-renewal allows HSCs to divide and give rise to both identical stem cells and more committed progenitor cells. This ensures the continual presence of a pool of HSCs throughout an individual’s life, providing a source for the generation of various blood cell types. The balance between self-renewal and differentiation is tightly regulated to sustain the HSC population while producing the necessary blood cells for the body.

After HSCs…

There are intermediate stages between hematopoietic stem cells (HSCs) and the more committed progenitor cells. These intermediate cells are often referred to as multipotent progenitors (MPPs), and they can be further classified into short-term and long-term MPPs based on their differentiation potential and self-renewal capacity.

1. Multipotent Progenitors (MPPs):
   • MPPs represent a population of cells that are more committed than HSCs but still retain multipotency, meaning they have the potential to differentiate into multiple blood cell lineages.
   • MPPs are often categorized into short-term MPPs (ST-MPPs) and long-term MPPs (LT-MPPs) based on their self-renewal and differentiation capabilities.
2. Short-Term Multipotent Progenitors (ST-MPPs):
   • ST-MPPs have a more limited self-renewal capacity compared to LT-MPPs.
   • They are more committed and poised to differentiate into various lineage-restricted progenitors and, ultimately, mature blood cells.
3. Long-Term Multipotent Progenitors (LT-MPPs):
   • LT-MPPs have a greater self-renewal potential compared to ST-MPPs.
   • They represent an intermediate stage between HSCs and more committed progenitors, playing a role in maintaining the pool of multipotent cells in the hematopoietic system.

The presence of MPPs in the hematopoietic hierarchy highlights the stepwise progression from HSCs to fully differentiated blood cells. The transition through MPP stages allows for a controlled and gradual commitment to specific lineages while maintaining a reservoir of cells with multipotent potential.

After MPPs…

Here’s a simplified overview of the differentiation pathways leading to progenitor cells:

1. Common Myeloid Progenitor (CMP):
   • Common myeloid progenitors are derived from HSCs and are committed to the myeloid lineage. Myeloid cells give rise to red blood cells, platelets, and various types of white blood cells (except lymphocytes).
   • CMPs can further differentiate into more lineage-restricted progenitors, such as megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs).
2. Megakaryocyte-Erythroid Progenitor (MEP):
   • MEPs are committed to the erythroid (red blood cell) and megakaryocytic (platelet) lineages.
   • MEPs can differentiate into erythroid progenitors and megakaryocyte progenitors.
3. Granulocyte-Macrophage Progenitor (GMP):
   • GMPs are committed to the granulocytic (neutrophils, basophils, eosinophils) and monocytic (macrophages) lineages.
   • GMPs can further differentiate into more mature progenitors that eventually give rise to differentiated cells of the granulocytic and monocytic lineages.
4. Common Lymphoid Progenitor (CLP):
   • Common lymphoid progenitors are committed to the lymphoid lineage, giving rise to various types of lymphocytes, including T cells, B cells, and natural killer (NK) cells.
   • CLPs can further differentiate into more restricted lymphoid progenitors, leading to the development of T cells, B cells, and NK cells.

Next Topic: Immune Cells Derived from the Various Progenitor Types

Source: ChatGPT response prompted and edited by Joel Graff.

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