Cell Differentiation How cells specialize to become tissues and organs

Current Research in Cell Differentiation Anthony Atala – researcher on growing new organs. Able to grow a bladder Has a dot matrix printer that prints out a heart.

For simple, hollow organs such as the bladder and trachea, researchers seed scaffolds with living cells and then transplant the entire organ into patients

July 13, 2012, Hannah Warren, 2, poses with her parents Lee Young-mi and Darryl Warren at Seoul National University Hospital in Seoul, South Korea.

The stem cells used came from Hannah's bone marrow through her hip bone. They were then seeded in a lab onto a plastic scaffold, where it took a week for them to multiply and make a new windpipe.

Dr. Doris Taylor University of Minnesota researcher. You can use detergents to remove all of the cells from connective tissue. She is holding a heart that has had all of the cells removed. She has been able to place cells on these hearts and have the cells grow and form a new heart. She has even been able to make one that beats!

Liver Buds Human skin stem cells, reprogrammed into an embryonic state and mixed with 2 other cell types formed miniature livers that kept mice alive for a few months.

Researchers have also worked to create pure cultures of functional cells in the laboratory, hoping that cells could be infused into patients, where they would establish themselves.

3 current Strategies: 1. Seed scaffolds with living cells and then transplant entire organ 2. Create pure cultures of cells and infuse into patients. 3. Grow and combine cell types together and then transplant. spray on skin spray on skin

Cells Cells specialize and organize themselves into tissues. These are the four types of tissues found in humans What type of tissue makes up the blood?

Tissues Tissues organize themselves into organs So, an organ is different types of tissues working together to do a job. In the case of the heart, there is muscular, connective, nervous and epithelial tissue in the heart working together to pump blood to the body.

How a cell decides what it will become Some of the signals that determine what a cell becomes comes from the cell itself. Depending on where the cell is certain genes will be turned on and others turned off. This will help determine the kind of cell it becomes.

External Factors in Cell differentiation Chemicals coming from other cells can influence what a cell becomes. These chemicals usually come from cells that are close by The chemicals emitted turn on and off certain genes.

Environmental Signals Cells also get signals from the environment. Temperature can be a factor that affects cells. Heat Shock can cause cells to produce proteins (HSP) to protect them from heat. Lack of oxygen, pH, UV radiation are other factors that can affect what genes are turned on by a cell.

Stem Cells This is a photo of a human stem cell growing on a culture medium This cell has the potential to become any cell in the human body. All of the specialized cells have the same DNA as the Stem Cell.

Fat cells

Nerve cells

Specialized cells of the retina

Macrophage

Fertilization and the Zygote If a cell is taken from the Morula stage it can become a person. The cell is totipotent If the cell is taken from the blastocyst stage it can become any organ, but it cannot become a person. Those cells are pluripotent

Unipotent Once a human cell starts down a path to become a specialized cell it cannot go back. For us the cell cannot become anything else, but that particular specialized cell. At this stage the cell is unipotent.

Regeneration There are some creatures who have cells that can go backward. That is they can go from unipotent to pluripotent For the salamander some of the cells in its leg can dedifferentiate. Those cells can become stem cells and then specialize into tissues to form a new leg.

This Sea Star is regenerating it lost limbs

The salamander can regenerate the limb, heart, tail, eye tissues, kidney, brain and spinal cord through out life

The Zebra fish can regenerate heart tissue

Deer regenerate their antlers every year. For a white tailed deer this can be 60 lbs.

The Snow shoe hare can regenerate parts of its ears.

The Brown Bat can regenerate parts of its wings

Crayfish can regrow lost claws.

Sea squirts can regrow a whole new animal

Gecko’s can regenerate their tails.

One third of the human liver can regenerate into a whole organ

This patient has received a liver transplant. It will take up to 6 months for the liver to regenerate completely

Internal Cues The cells position in the blastula helps to determine what it will become as the blastula turns into the gastrula. Cells on the outside of the gastrula become what’s called ectoderm. Cells on the inside become what is called endoderm. The middle germ layer is called the mesoderm.

General fates of the three germ layers

Gene Regulation All cells start out with the same # of chromosomes and the same # of genes. For a stem cell to become a smooth muscle cell it must turn on the smooth muscle genes and turn off the others.

Internal cues Where the stem cells is helps to determine which genes are turned on and off. One of the internal cues is transcription factors. Transcription factors are proteins, made in the cell, that turn genes on. So where the cell is can cause particular proteins to be made that help to turn genes on.

Male and Female Up to 5 weeks in development the male and female fetuses look the same. At that point the testes start producing a transcription factor. This protein, called the SRY factor is produced in the testes. It flows from cell to cell and turns on The SRY gene in the Y chromosomes of the males. This gene causes a fetus to develop as a male. So, until about 6 weeks in development we are all females!

Heat Shock Factor- External cues When a cell is too hot it produces heat shock factor (HSF). This protein goes to the nucleus. It turns on certain genes to produce compounds that will make the cell membrane resistant to heat.

Other external factors Similar shock factors have been discovered for lack of oxygen (hypoxia). So cells have a number of fates. They are affected by their location, the cells next to them and external factors like heat and oxygen. These whitefish cells are in the morula stage. What is their potency?