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The Biology of Stem Cells

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THE BIOLOGY OF STEM CELLS
Melissa Henriksen, PhD
Clare Boothe Luce Assistant Professor
Biological Sciences
The Biology of All Cells
transcription
translation
DNA
mRNA
Protein
3’polyA tail
5’cap
Gene Expression
transcription
DNA
translation
mRNA
Protein
Different Cell Types
pancreatic
bone
neurons
ES
Same DNA
Different Gene Expression
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?
Somatic Cell
Two identical daughters
Stem Cell
Self-renewal
Differentiate
Potency
The range of commitment options available to a cell
• Totipotent
• Pluripotent
• Multipotent
• Oligopotent
• Unipotent
Potency
Potency
Pluripotent
Multipotent
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
Amniotic
Adult
Somatic Cell Nuclear Transfer
DOLLY
1997
“Decisions”
not irreversible
SCNT & Animals
SCNT & Humans
SCNT & Humans
?
SCNT & Cancer Cells
Melanoma
Tetraploid Complementation
E9.5
Pluripotent Stem Cells
start with cancer cell
Breast cancer
Leukemia
Lymphoma
Melanoma
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
Goal: Manipulate a somatic cell’s potency
• Totipotent
Potency
• Pluripotent
• Multipotent
• Oligopotent
• Unipotent
somatic cell
Molecular Reprogramming
• Cell Fusion
пѓј pluripotent
• Cell Extract
x pluripotent
• Cell Explantation
пѓј pluripotent
• Add Four Factors
пѓј pluripotent
+ 4 Factors
Bibliography
• AFS
• SCNT
– Cancer cells
•
•
•
•
ANT
Blastomere
Parthenogenesis
Molecular Reprogramming
–
–
–
–
Cell Fusion
Cell Extract
Cell Explantation
Defined Factors
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