endothelial to hematopoietic transition

Definition

Target type: biologicalprocess

The generation of hematopoietic stem cells from hemogenic endothelial cells by a process that includes tight-junction dissolution and loss of cell polarity followed by delamination from the endothelium. [PMID:20154732, PMID:22521721]

Endothelial-to-hematopoietic transition (EHT) is a fundamental process in embryonic development, whereby endothelial cells, which line blood vessels, transform into hematopoietic stem and progenitor cells (HSPCs), the origin of all blood cells. This remarkable transition ensures the formation of a functional circulatory system and establishes the hematopoietic system, which sustains blood production throughout life.

EHT is a complex and tightly regulated process involving a series of molecular events that reprogram endothelial cells, leading to the loss of their vascular identity and the acquisition of hematopoietic characteristics. This transformation can be broadly divided into three stages:

1. **Endothelial cell specification:** The process starts with the specification of a subset of endothelial cells within specific vascular niches, usually in the aorta-gonad-mesonephros (AGM) region, the yolk sac, and the placenta in mammals. These endothelial cells display unique molecular markers and are predisposed to EHT.

2. **Hematopoietic commitment:** Once specified, these endothelial cells undergo a commitment phase where they gradually lose their endothelial characteristics and acquire hematopoietic potential. This involves the downregulation of endothelial genes and the upregulation of hematopoietic genes, guided by specific transcription factors and signaling pathways.

3. **Hematopoietic differentiation:** The committed hematopoietic progenitor cells then differentiate into various lineages of blood cells, including erythrocytes, leukocytes, and platelets. This differentiation process is governed by a complex interplay of growth factors, cytokines, and transcription factors.

**Molecular Mechanisms Underlying EHT:**

* **Transcription factors:** Several transcription factors play crucial roles in regulating EHT. These include SCL/TAL1, GATA1, RUNX1, FLI1, and PU.1, which control the expression of genes involved in endothelial specification, hematopoietic commitment, and lineage differentiation.
* **Signaling pathways:** Specific signaling pathways, such as Notch, Wnt, VEGF, and BMP, are involved in regulating EHT. These pathways interact with each other and with transcription factors to fine-tune the process.
* **Epigenetic modifications:** Changes in DNA methylation and histone modifications contribute to the reprogramming of endothelial cells during EHT. These modifications alter the accessibility of genes, regulating gene expression and guiding cell fate decisions.

**Clinical Relevance:**

* **Hematopoietic stem cell transplantation:** Understanding EHT has significant implications for hematopoietic stem cell transplantation, a life-saving treatment for various hematological malignancies and genetic disorders. The ability to generate HSPCs from endothelial cells could provide an alternative source for transplantation.
* **Hematopoiesis in disease:** Dysregulation of EHT has been implicated in various hematological disorders, including leukemia, myelodysplastic syndromes, and aplastic anemia. Understanding the underlying mechanisms could lead to new therapeutic strategies for these diseases.

In conclusion, EHT is a crucial developmental process that establishes the hematopoietic system, essential for blood cell production. Elucidating the intricate molecular mechanisms underlying this transition has implications for advancing our understanding of hematopoiesis, improving stem cell-based therapies, and developing new strategies for treating hematological disorders.'"

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