STEM CELLS Image Credit: Mesenchymal precursor cellsMesenchymal precursor cells

Division and differentiation  All cells reproduce by dividing  Cells produced by mitosis are clones  This is how unicellular organisms reproduce asexually  Multicellular organisms are a bit different  When the cells of an embryo divides, initially they are all the same  Later the cells start to differentiate (specialise) © 2010 Paul Billiet ODWSODWS Released into the Public Domain by JrockleyJrockley Image Credit:

Differentiation and gene expression  All the somatic cells (not gametes) of a multicellular organism contain the same genetic information  But cells in different tissues perform different functions  Cells in different tissues have quite different forms  Therefore, some genes are expressed in a cell and not others © 2010 Paul Billiet ODWSODWS

Hox genes  Genes that control development are a group called Hox genes  Surprisingly similar for all animals  The sequence in which they express seems to create the differences in development Image Credit: Hox genes of fruit fly and mouseHox genes of fruit fly and mouse © 2010 Paul Billiet ODWSODWS

What causes differentiation?  Cells differentiate according to their position in an embryo  Transferring cells from one place to another illustrates this  The signals are called growth factors  These factors are released by zones of cells called organisers  The surrounding cells develop along a determined route Zebra fish embryology © 2010 Paul Billiet ODWSODWS

Early experiments  Displace organiser cells and the embryo will develop an organ in a different place from usual  Or if a second organiser is added an additional organ will develop Copyright© 2006 Nature Publishing Group Nature Reviews Molecular Cell Biology © 2010 Paul Billiet ODWSODWS

Totipotent and pluripotent cells  In simple animals (e.g. sponges) the cells retain their capacity to regenerate into whole new sponge  Totipotent  More complex animals lose this capacity  Cells of the early embryo are capable of turning into any type of cell (pluripotent)  Differentiated cells may not be able to do this Image Credit: Sea SpongeSea Sponge © 2010 Paul Billiet ODWSODWS

Stem cells  Cells that can develop into any other cell are called stem cells  A few still exist in the body of an adult  E.g. bone marrow has blood stem cells  E.g. umbilical cords have stem cells Bone marrow stem cells © David DarlingDavid Darling © 2010 Paul Billiet ODWSODWS

Image Credit: Blood stem cell differentiationBlood stem cell differentiation

Making stem cells  Stem cells could be used to replace tissues that are damaged or diseased  E.g. cardiac muscle will not divide once it has differentiated  Stem cells stimulated to grow into cardiac cells could replace the need for heart transplants  The problem of tissue typing and tissue rejection still remains  Implanted tissue could become cancerous © 2010 Paul Billiet ODWSODWS

Cloned stem cells  If stem cells can be cloned from the cells of a patient they can be used to generated genetically identical tissues  Therapeutic cloning  Mammalian cells need to be set back to the beginning of the cell cycle (G 0 ) © 2010 Paul Billiet ODWSODWS

Somatic cell nuclear transfer  SCNT  Made famous by Dolly the sheep  Oocytes (unfertilised egg cells) harvested  Nuclei removed  Somatic cells from animal to be cloned fused with enucleate oocyte  Electric shock sets the cell cycle to G 0  Nuclear genome cloned but…  Mitchondrial genome comes from animal which donated the oocyte Image Credit: Removing the nucleus from an oocyteRemoving the nucleus from an oocyte © 2010 Paul Billiet ODWSODWS

Problems for SCNT in therapeutic cloning  Human oocytes are few and difficult to obtain  A lot of oocytes needed to generate successful cell lines (304 oocytes from 14 macaques to produce 2 cell lines)  Ethical problem of embryo destruction  Early embryo cells are harvested to generate cloned tissues for transplants/grafts © 2010 Paul Billiet ODWSODWS

The answers?  Fuse somatic cell with enucleated oocyte of another species of animal  Umbilical cord stem cells  Induced pluripotent stem cells (iPS) (Genetically modified somatic cells reprogrammed back to its undifferentiated state) Image Credit: Umbilical cordUmbilical cord © 2010 Paul Billiet ODWSODWS