40.6 : Lineage Commitment

Commitment is the process whereby stem cells:

1. lose their ability to form all cell types and
2. irreversibly change into a specific type.

The multipotent hematopoietic stem cells, (HSCs), differentiate into the multipotent hematopoietic progenitor cells, (HPCs). The HPCs express many lineage-specific cytokine receptors. Each of these receptors binds specific cytokines, activates distinct signaling pathways, and expresses a particular gene set. The HPCs further differentiate to form committed progenitors, forming either common myeloid progenitors (CMPs) or common lymphoid progenitors (CLPs). The CMPs and CLPs proliferate, self-renew, and further differentiate into mature blood cells and immune cells depending on the receptors they express and the specific cytokines that bind. For example:

• Thrombopoietin (TpoR)- They help progenitors differentiate into megakaryocytes or platelets.
• Erythropoietin (EpoR)-These receptors promote the development of erythrocytes.
• Macrophage-colony stimulating factor (M-CSFR)-These receptors regulate the formation of macrophages.
• Granulocyte-colony stimulating factor (G-CSFR)- They help HPCs differentiate into granulocytes.
• Interleukin-7 receptor (IL-7R)- They help progenitor cells become lymphocytes.

Thus, lineage commitment helps HSCs lose their multipotency and differentiate into more restricted cell fate.