iPSC Flashcards
Who discovered iPSC and when?
Yamanaka in 2006
What is an intrinsic factor that is capable to produce cell differentiation to muscle cells?
MyoD
What are the 4 prerequisites for Yamanaka’s discovery?
1) Disposal of idea that cell differentiation is irreversible
2) Nuclear reprogramming research showing that factors in oocyte can induce reprogramming in somatic nuclei to pluripotent cells
3)Trans-differentiation induced by MyoD
4) Discovery of cell culture conditions and molecular pathways driving ESC self renewal
What are the Yamanaka factors?
Oct 3/4, Sox2, Klf4, cMyc
What are potential applications for iPSCs?
Disease modeling, personal medicine, cellular regeneration, bone regeneration, gene targeting
What are the limitations of iPSCs?
Low reprogramming efficiency; Genomic instability; Oncogenic transformation
what are the two delivery methods of yamanaka factors
integrative and non-integrative system
how are pluripotency and cellular identity controlled?
Exclusively by epigenetic regulatory mechanisms
What is cellular identity?
A specific molecular state that is stabilized and maintained through
cooperating transcriptional and epigenetic mechanisms
Example: neuron, muscle cell, skin stem cell, ES cell
What happens during early reprogramming?
“Modular” transcriptional programmes are induced by OSKM factors; Changes in metabolism (oxidative phosphorylation to glycolisis); down-regulation of somatic cell identity genes
How is the bivalent character of developmental genes achieved?
By the simultaneus activity of the PcG (for repressive) and TrxG (for activation)
What is an important step during early reprogramming of fibroblasts into iPS cells?
A. The induction of genes involved in differentiation programs.
B. The transition from a mesenchymal to an epithelial fate.
C. The establishment of bivalent chromatin.
D. Expression of fibroblast-specific genes.
B
What forms a mediator-bound super enhancer?
Yamanaka factors, Nanog and distal enhancers leading to open chromatin
What are other requirements for pluripotencY?
Erasure of methylation, reactivation of silent X chromosome, re-establishment of bivalent chromatin on developmental genes
