1. Cell Differentiation and Regeneration The number of cells from any organism ranges from one to trillions. However, even the most complex organisms have a relatively small (~200) catalog of differentiated cell types with specialized function (bone, muscle, nerve). Cell differentiation: the process by which an undifferentiated cell reaches its specialized function. It occurs during histogenesis. Cell differentiation is stable. Most differentiated cells cannot transform into other cell types (it can happen during regeneration). Red and white blood cells in a large vessel

2. Cell division and differentiation Cell differentiation occurs continuously in adult organisms. Most organisms live much longer than the individual cells from which they are composed. As cells die, new cells differentiate for replacement. The rate of cell turnover differs dramatically in different tissues. The lining of the small intestine is completely replaced every few days. However, neurons are long lived and don’t recycle. Differentiated cells are produced by 2 methods: 1. Some differentiated cells divide. Hepatocytes are liver cells that make bile and detoxify chemicals. They are long lived and divide slowly. However, after damage by toxins or injury, hepatocytes grow rapidly. If you remove 2/3 of the liver, it regenerates in 1-2 weeks.

3. Stem cells Stem cells have 3 properties: 1.They are undifferentiated. 2.They have a capacity for self renewal and divide slowly. 3.They form committed progenitor cells that divide a few times but are committed to form a specific tissue. Renewal by stem cell differentiation is common (blood cells, epithelia, and spermatogonia). Stem cells are usually hidden in a safe, sequestered site away from injury. Stem cells of the intestine lie at the base of the Crypts. They continuously release committed progenitor cells that form the intestinal villi. 2. Other differentiated cells arise from a pool of undifferentiated stem cells.

4. Differentiation of blood cells Hematopoiesis: (hemat = blood, poien = to make), the blood of vertebrates contains many different types of cells with distinct functions. All mature blood cells are short lived and must be replaced continuously from stem cells. In humans, the hematopoietic stem cells produce billions of blood cells each hour to replace the aging cells. Hemangioblast: an embryonic stem cell that gives rise to blood vessels and universal blood stem cells. Universal blood stem cells: form myeloid and lymphoid precursors. Myeloid precursors form several types of differentiated cells including red blood cells which transport O 2 and CO 2. They also make platelets for coagulation of blood, and monocytes / granulocytes that serve a protective role. Lymphoid precursors make lymphocytes that are involved in B and T cell immunity.

5. The overall scheme for hematopoiesis. The embryonic stem cell, the hemangioblast, gives rise to angioblasts that make both vessels and universal blood stem cells. The universal stem cells renew and also form the myeloid and lymphoid precursors.

6. How is hematopoiesis regulated? Blood cells and vessels are derived from mesoderm. BMP-4 is a protein that promotes ventral development. It combines with other cytokines including fibroblast growth factor and activin to induce hematopoesis. The SLC gene was discovered as over expressed in human leukemia, and it appears to be required early in the process of stem cell development. Knock out the gene in mice = they fail to form blood cells. Pluripotent stem cells and progenitor cells express transcription factors/switch genes that direct pathways of differentiation. GATA proteins regulate the decision to form progenitors or remain as stem cells. GATA-1 induces RBCs. GATA-2 blocks RBC differentiation and induces stem cells. Colony stimulating factors (CSF-1) are cytokines that direct expression of specific transcription factors for myeloid cells.