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Blood  - Development and Stem Cells


Embryonic Development of the Blood:

Vertebrate blood development occurs in two phases. A transient embryonic (“primitive”) phase of hematopoiesis, beginning on E7.5 in the mouse embryo, is followed by the definitive (“adult”) phase, which begins on E9.5 in the liver of the developing mouse embryo. The embryonic phase of hematopoiesis is thought to initiate the circulation that provides the embryo with its initial blood cells and with its capillary network connecting it to the yolk. The definitive phase of hematopoiesis generates more cell types and provides the stem cells that will last throughout the vertebrate's lifetime.

In the mouse embryo, red blood cell formation, or erythropoiesis, is seen in the blood islands in the mesoderm surrounding the yolk sac. However, the embryonic hematopoietic cell population is transitory. The hematopoietic stem cells that last the lifetime of the organism form within nodes of the mesoderm that line the mesentery and the major blood vessels. The aorta-gonad-mesonephros (AGM) region in the aortic wall appears to be the most important source of new blood cells, and it has been found to contain numerous hematopoietic stem cells by day 11 of mouse embryonic development.  These hematopoietic stem cells later colonize the liver and constitute the fetal and adult circulatory system. Near the time of birth, stem cells from the liver populate the bone marrow, which then becomes the major site of blood formation throughout adult life.

Embryonic and Postnatal Development of the Blood

In the adult bone marrow, Hematopoeitic Stem Cells (HSCs) follow a multistep irreversible developmental program which ends in the differentiated various cells of the blood. Exact timing and sequential order of all choices in each cell underpin normal hematopoiesis. HSCs contain self-renewal capacity and apparently give rise to multipotent progenitors these cells further give rise to oligopotent progenitors which are Common Lymphoid Progenitors (CLPs) and Common Myeloid Progenitors(CMPs).

Diversification of myeloid and lymphoid pathways follows this stage. CLPs are the most primitive common precursor for T and B lymphocytes and CMPs advance to Megakaryocyte/Erythrocyte Progenitors (MEPs), Granulocyte/Macrophage Progenitors (GMPs), and Dendritic Cell (DC) progenitors.

Each of these progenitor cells follow a different pathway to become extremely specific blood cells. The CLPs differentiate finally into T helper, T cytotoxic and T regulatory cells after leaving the bone marrow to the thymus or into mature B cells in the bone marrow. The cells from the CMP differentiate into erythrocytes, granulocytes and DC type I and DC type II.

Blood formation in the human embryo begins in the liver at about week 5 and at week 12 in the spleen, red bone marrow, and thymus.

Data from two external large scale datasets was added to cells of the blood lineage. The Hematopoietic Fingerprints and the HaemAtlas dataset. In Lifemap, the HaemAtlas dataset provides gene expression for adult human B cells, helper T cells, natural killer cells, granulocytes, and monocytes while the Hematopoietic Fingerprints dataset provides gene expression information for postnatal stem cells and their progeny.