THE BIOLOGY OF STEM CELLS

The Biology of All Cells DNAmRNAProtein transcriptiontranslation 3’polyA tail

Gene Expression DNAmRNAProtein transcriptiontranslation

Different Cell Types Same DNA Different Gene Expression pancreaticboneneurons ES

The Biology of Stem Cells Embryonic Stem Cells The Concept of Potency Adult Stem Cells Advances in Stem Cell Science

Human Embryogenesis

Embryonic Stem Cells & IVF Stem Cell Research

Commitment in Embryogenesis Cell Commitment Cells make “Decisions” “Decisions” determine cell’s fate Thought to be irreversible

Differentiation occurs in three stages Fertilized animal eggs and early embryonic cells can give rise to all the different cell types of the body, they are considered “totipotent.” – Identical twins Cell fates become progressively restricted during development, a process called “differentiation.” Differentiation occurs in three stages – Specification Fate is not absolute Cell identity subject to change – Determination Fate is fixed, and cannot change in response to environment – Differentiation Changes in cell structure and function

The Blastocyst

Culturing Embryonic Stem Cells

What is a Stem Cell? Two identical daughters Self-renewal Differentiate Somatic Cell Stem Cell

Life Sciences-HHMI Outreach. Copyright 2006 President and Fellows of Harvard College. Self-renewal Stem Cell CellStem Differentiation

Potency The range of commitment options available to a cell Totipotent Pluripotent Multipotent Oligopotent Unipotent Potency

PluripotentMultipotent

Adult Stem Cell Differentiation

Adult Stem Cell Plasticity

Amniotic Fluid-derived Stem Cells

Potency The range of commitment options available to a cell Totipotent Pluripotent Multipotent Oligopotent Unipotent Potency Embryonic Adult Amniotic

Somatic Cell Nuclear Transfer DOLLY 1997 “Decisions” not irreversible

Two types of cloning: reproductive and therapeutic ECB Reproductive cloning has been accomplished for large mammals, not humans Therpeutic cloning in humans reported two months ago Somatic nucleus must be reprogrammed to embryonic program by egg cytoplasm Somatic cell nuclear transplant (SCNT)

SCNT & Animals

SCNT & Humans

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SCNT & Cancer Cells start with cancer cell Breast cancer Leukemia Lymphoma Melanoma Pluripotent Stem Cells Melanoma Tetraploid Complementation E9.5

Advances in Stem Cell Science Avoid ethical issues Egg donation Matched stem cells Develop cell-based disease models Understand the science Parthenogenesis 8-cell Blastomere Altered Nuclear Transfer Molecular Reprogramming

Cells of early mammalian embryos are “totipotent” Totipotency “lost” during development and differentiation (~16 cells in mouse) 8-cell mouse embryos Culture in vitro to “blastocyst” Aggregate in vitro Implant into hormonally- primed female for gestation and birth Tetraparental “chimeric” pup

Molecular Reprogramming Potency Goal: Manipulate a somatic cell’s potency Totipotent Pluripotent Multipotent Oligopotent Unipotent somatic cell

Molecular Reprogramming Cell Fusion Cell Extract Cell Explantation Add Four Factors pluripotent + 4 Factors pluripotent x pluripotent

Misconceptions Pregnancy, fetuses or babies are aborted or harmed in stem cell research. Fact: Fertilized Blastocysts donated from IVF labs are used and no pregnancy is aborted. The fertilized embryos are removed from women’s bodies and used for research. Fact: The embryos are left over from IVF and are frozen and are not implanted for pregnancy.

Misconceptions A clone is grown in a lab without an embryo or born from a mother and is the same age and personality as you, and has no belly button. Fact: a clone would need a fertilized embryo and would have to be implanted in a woman’s uterus. If you were cloned at 14, the clone would be 14 years younger than you (a baby you) and would have to have a mother to be born, so yes, it would have a belly button.

Misconceptions If the embryos were not used in stem cell research they would have been used to make children. Fact: The embryos left over from IVF are discarded. Men and women who donate their embryos do not know that their embryos are used for research. Fact: The embryos used in scientific research are donated with written and informed consent (permission) by the donors.

Future Applications Stem Cells may one day help scientists to regenerate cells lost in diseases like: Repair heart muscle after a heart attack Pancreas cells lost in diabetes Neurons lost in Alzheimer’s Retinal cells causing blindness Understand the cell growths of cancers Help organ transplantation