RK Lectures 58-59: Cell Differentiation, Stem Cells, and Reprogramming Flashcards
What are the steps on the way to a fully differentiated cell?
- uncommitted precursor cell (cells with more than one possible fate)
- determination (the process whereby a cell becomes committed to a single lineage and acquires the competence to undergo terminal differentiation)
- differentiation (cell acquires cell type-specific properties
List the events associated with myoblast differentiation.
- exit from cell cycle
- expression of muscle-specific genes
- fusion to form multinucleated myotubes
- expression of ACh receptors and other proteins of the neuromuscular junction
Where do muscle cells come from?
skeletal muscle cells derive from precursors found in the dorsal halves of somites
Describe the roles in sequence of the MyoD family of muscle regulatory factors.
Myf5 and MyoD are used for determination (somatic cell to myoblast)
MyoD myogenin and MRF4 are used for differentiation (myoblast to terminally differentiated myofiber)
Describe the role of positive feedback in cell differentiation.
- secretion of factors such as Wnts and SHH
- induction of expression of Myf5 and MyoD in precursor cells of dorsal somites resulting in commitment to the skeletal muscle lineage
- MyoD maintains its own expression (stability of determined state)
- Induction of myogenin expression
- activation of specific Mef2 genes
- enhancement and maintenance of Mef2 and myogenin expression leading to amplification and maintenance of the differentiation process
Describe the series of events that occur when cultured myoblasts are transitioned from growth factor rich medium to a growth factor depleted medium.
A1. decrease in CyclinD1/Cdk4 activity
A2. decrease in phospho-pRb
A3. exit from cell cycle
B1. increase in MyoD transcriptional activity B2. increase in p21 expression B3. decrease in Cyclin E/Cdk2 activity B4. decrease in phospho-pRb B5. exit from cell cycle
What are stem cells?
cells that can self-renew and generate differentiated cell types
What are adult stem cells?
responsible for homeostatic maintenance and repair to injury (e.g. hematopoietic stem cells, skeletal muscle satellite cells)
What are embryonic stem cells?
cells derived from the inner cell mass of the blastocyst that have been placed into culture
can divide indefinitely and differentiate into all lineages of the three germ layers in vitro and in vivo
What is unipotency?
the ability to form a single cell type or lineage (e.e. testes stem cells)
What is multipotency?
the ability to give rise to multiple cell types (e.g. hematopoietic stem cells)
What is pluripotency?
the ability to give rise to all cells of the embryo (e.g. ES cells)
EXCLUDES extraembryonic tissues
What is totipotency?
ability to give rise to all cells of an organism, including embryonic and extraembryonic tissues (e.g. zygotes)
What is Somatic cell nuclear transfer (SCNT)?
transfer of a somatic nucleus into an enucleated oocyte
What is reproductive cloning?
generation of a new organism following SCNT or other means (e.g. Dolly the sheep)
