THE BIOLOGY OF STEM CELLS Melissa Henriksen, PhD Clare Boothe Luce Assistant Professor Biological Sciences

The Biology of All Cells DNAmRNAProtein transcriptiontranslation 5’cap 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

The Blastocyst

Culturing Embryonic Stem Cells

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

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

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

Parthenogenesis Asexual Reproduction Normal in Reptiles; Not seen in Mammals Trick human eggs to undergo in the lab Immunologically matched to egg donor “Universal Donor?” Not Viable No “Potential Human Being”

8-cell Blastomere PGD - Preimplantation Genetic Diagnosis 1 of 8 cells removed ACT cultured embryonic stem cell line from one cell

Altered Nuclear Transfer Idea suggested by President’s Council on Bioethics Apply a genetic trick in the somatic cell nucleus Blastocyst generated is not viable No “Potential Human Being” Proof-of-Principle demonstrated in mice by scientists at MIT’s Whitehead Institute

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

Bibliography AFS SCNT –Cancer cells ANT Blastomere Parthenogenesis Molecular Reprogramming –Cell Fusion –Cell Extract –Cell Explantation –Defined Factors