ne102 3/20 lecture - transcription regulation; rewriting development, to generate better tools

how does cell differentiation happen?

undifferentiated stem cells use specific TRs → specialized/differentiated cell

types of embryonic stem cells

totipotent, pluripotent, multipotent

from stem cells to differentiated cells

unfertilized zygote → blastocyst → gastrula (mesoderm, ectoderm, endoderm, gametes)

totipotent stem cells

zygote → embryo + can become placenta

pluripotent stem cells

in blastocyst, embryo + any cell type (NOT placenta)

multipotent stem cells

in lining of gastrula; mesoderm, endoderm, ectoderm + found in umbilical cord

non-embryonic stem cells (adult stem cells)

organs repair + differentiated cells

combinatorial control

during first stages of dev only a few TRs are used to control expression # of proteins needed in developing cells at that time (+ inducing transcription of TRs needed for following step)

cell differentiation process in gurdon’s

zygote (egg cell unfertilized w/ nucleus replaced w intestine cell’s) → expressed TR X → blastocyst → tadpole

cell memory

each TR induces its own expression to get to specific cell types

what loop is cell memory?

positive feedback, TFs can activate their own transcription in absence of a stimulus

how to convert one cell kind into a different one?

cell specific transcriptional regulators can convert one cell kind to a diff one (ex: liver cells → neuron by neuro-specific TRs)

iPSCs

induced pluripotent stem cells (like blastocyst ones) from differentiated cells

reprogramming differentiated cells into stem cells

genes encoding 3 TRs needed in blastocyst introduced into fibroblast → cells allowed to divide in culture (iPS cell) → cells induced to differentiate in culture w/ specific TRs

specific factors that maintain embryonic stem cell identity

Oct3/4, Sox2, klf4

takahashi/yamanaka experiment

genes encoding 3 TRs injected in fibroblast → iPSCs → injected into blastocyst → embryo formation + development in mice