Transcript B1510_module5-2_Cloning_StemCells_2011

5-2a: Cloning
• How are mammals cloned?
• What is the difference between reproductive
cloning and therapeutic cloning?
Hello, Dolly!
Dolly and her surrogate mother
Roslin Institute
Dolly and her lamb, Bonnie
Roslin Institute
Mammalian cloning
via somatic cell
nuclear transfer
Anne McLaren, 2001 Nature 414,
129-131 doi:10.1038/35102194
Why has cloning mammals become
possible now?
• In vitro fertilization technology has come of
age. Louise Brown the first “test tube
baby” was born in the 1970s.
• Nuclear transfer into human eggs is
possible for males with defective sperm.
• Embryo transfer is routinely used for
reproduction of livestock (cattle)
How easy (efficient) is animal
reproductive cloning?
Dolly was the only lamb from 277 fused eggs
Many animal species have been cloned.
Tetra – rhesus
monkey
Copycat
Idaho Gem mule
http://www.businesspundit.com/20-animals-that-have-been-cloned/
Are cloned animals healthy?
Dolly gave birth to a healthy lamb named Bonnie.
Dolly suffered prematurely from arthritis and other
ailments of old age.
Dolly’s telomeres (ends of chromosomes) were
shorter than for other sheep of comparable age.
Complications in reproductive cloning
• Cloned offspring syndrome
– Placental abnormalities
– Fetus too large
– High rate of spontaneous abortions
– Early death
• Shorter telomeres?
• Genes not imprinted properly
– Genes that control placental growth, fetal
growth inactivated in maternal chromosomes
Therapeutic cloning produces embryonic
stem cells
Embryonic stem cell colony
5-2b: Stem Cells
• What is the difference between embryonic
stem cells and adult stem cells?
• What legal and ethical issues revolve around
cloning and stem cell technologies?
Stem cells: undifferentiated cells that
can keep dividing to replenish various
differentiated cell populations
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Totipotent – embryonic stem cells
Pluripotent – bone marrow stem cells
Oligopotent – hematopoietic stem cells
Multipotent – erythropoietic stem cells
Unipotent – reticulocytes
Some adult stem cells
mammalan development in vitro from
egg to blastocyst
http://yaolab.stanford.edu/research/preimplantation.html
Human development through
blastocyst implantation
© 2001 Terese Winslow, http://stemcells.nih.gov/info/scireport/appendixA.asp
Generating embryonic stem cells for
regenerative medicine
Klimanskaya I, N Rosenthal, R Lanza 2008, Nature Reviews Drug Discovery 7, 131142 doi:10.1038/nrd2403
Alternatives to embryonic stem cells?
• Induced pluripotent stem cells
– Aoi et al. 2008, Generation of Pluripotent Stem
Cells from Adult Mouse Liver and Stomach
Cells, Science 321:699-702
– Retroviral vectors used to transduce 4
transcription factors, incl. c-Myc (protooncogene)
– ES-like cells in gene expression profile,
pluripotency (form tumors containing different
cell types, form all 3 major tissue types,
germline transmission)