myeloid leukocyte differentiation

Definition

Target type: biologicalprocess

The process in which a relatively unspecialized myeloid precursor cell acquires the specialized features of any cell of the myeloid leukocyte lineage. [GOC:add, PMID:16551251]

Myeloid leukocyte differentiation is a complex and tightly regulated process that gives rise to various mature myeloid cells, including neutrophils, macrophages, monocytes, eosinophils, basophils, and mast cells. This differentiation process begins with hematopoietic stem cells (HSCs) in the bone marrow, which have the potential to develop into all blood cell lineages.

HSCs commit to the myeloid lineage through a series of transcriptional and epigenetic changes, driven by specific transcription factors and signaling pathways. These changes lead to the expression of myeloid-specific genes and the suppression of genes associated with other lineages.

The first committed myeloid progenitor cells are called common myeloid progenitors (CMPs). CMPs can differentiate into megakaryocyte-erythroid progenitors (MEPs) or granulocyte-macrophage progenitors (GMPs). GMPs, as the name suggests, are the precursors for granulocytes (neutrophils, eosinophils, basophils) and macrophages/monocytes.

**Granulocyte Differentiation:**

GMPs give rise to granulocyte-monocyte progenitors (GMPs), which further differentiate into myeloblasts, promyelocytes, myelocytes, metamyelocytes, band cells, and finally mature granulocytes. Each stage is characterized by specific morphological changes, including the formation of granules and the development of a segmented nucleus.

* **Neutrophils** are the most abundant type of granulocyte and play a critical role in innate immunity by phagocytizing bacteria and fungi.
* **Eosinophils** are involved in parasitic infections and allergic reactions.
* **Basophils** are involved in allergic reactions and the release of histamine.

**Monocyte/Macrophage Differentiation:**

GMPs also give rise to monoblasts, which differentiate into promonocytes and then mature monocytes. Monocytes circulate in the blood and can differentiate into macrophages in tissues. Macrophages are highly phagocytic cells involved in engulfing pathogens, cellular debris, and apoptotic cells.

**Regulation of Myeloid Differentiation:**

The differentiation of myeloid leukocytes is tightly regulated by a complex interplay of transcription factors, cytokines, and signaling pathways.

* **Transcription factors:** Key transcription factors involved in myeloid differentiation include PU.1, GATA1, C/EBPα, and RUNX1. These factors regulate the expression of genes that control cell fate and differentiation.
* **Cytokines:** Cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF) play crucial roles in promoting the proliferation and differentiation of specific myeloid cell types.
* **Signaling pathways:** Signaling pathways such as the JAK-STAT, MAPK, and PI3K pathways are activated by cytokines and other stimuli, leading to the activation of downstream transcription factors and the regulation of gene expression.

The precise regulation of myeloid differentiation is essential for maintaining a balanced immune system. Dysregulation of this process can lead to various myeloid malignancies, including leukemia, lymphoma, and myelodysplastic syndromes.'
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