Lecture 31: Stem Cells Flashcards
Founder Stem Cells
- Each organ/tissue has a fixed number of founder cell poplutions programmed to have fixed number of divisions
- Controlled by short range signals that operate for a few hundred cell diameters
- Define the size of large final structures
- If the adult organ needs to be renewed, founder stem cells can divide as stem cells giving rise to one daughter cell that remains a stem cell and a set of cells tha have a set numebr of transit amplifying divisions
Transit Amplifying Cells
- Some characteristics of a stem cell and some of a differentiated cell
- Leave basal layer and are incorporated into the layers above
- They are programmed ot divide for limited number of times and then differentiate
Types of Stem cells
- embryonic stem cells
- Adult stem cells or tissue-specific stem cells
- Fetal stem cells
- Induced Pluripotent Stem Cells (iPS cells)
Embryonic stem cells
- Derived from the blastocyst stage of embryo
- Capable of proliferating indefinitely in cluture with unrestricted developmental potential
- Develop into different cell types with characteristics appropriate for that site
- If they are put back into blastocyt they can integrate well with the embryo
- but if they are injected into an embryo at a later stage or into an adult they fail to receive appropriate sequence of cues for proper differentiation
- often becoming a tumor
- but if they are injected into an embryo at a later stage or into an adult they fail to receive appropriate sequence of cues for proper differentiation
Embryonic stem cells and Teratomas
- ES cells give rise to disorganized growths called teratomas
- The defining feature of an ES cell is its ability to differentiate into a wide range of tissues
- Teratomas do not display axis formation or segmentation
- Unlike embryos, ES cells on their own are incapable of generating the body plan.
Application of Embryonic Stem Cells
- They are strong, reliable, and have highly reproducible data tha establishes pluripotency
- they provide a solid theoretical and experimental foundation to:
- Induce development of specialized cell types
- Solve rejection problems
- have good growth properties
- Promising “proof-of-principle” research
Successful Treatment of Animal models of Disease with mouse ES cell-derived Cells
- Severe immune deficiency
- Diabetes
- Parkinson’s disease
- Spinal injury
- Demyelination
- Myocardial infarction
What is somatic cell nuclear transfer
- Nucleus taken from somatic cell of patient and injected into oocyte of a donor replacing the oocyte nucleus
is immune rejection a serious problem in adult stem cells
yes (grafted cells are rejected by host if genetically different)
The key determinants of ES cell character are
gene regulatory proteins
gene regulatory proteins of ES cells
- Oct 3/4
- Sox 2
- Myc
- KIF 4
When gene regulatory protein (Oct 3/4, Sox2, Myc, and KIF4) are injected into a fibroblast it will become
ES like cell (though the yield is low and it is not identical to ES cell)
Transcription factors that are essential for establisment and maintenance of pluripotent stem cells in embryo,
- Nanog
- Oct4
- Sox2
- FoxD3
What transcription factor is required for early stages of pluripotent cell differentiation
- GCNF
___ and ___ are growth factors found in pluripotent cells
- Cripto
- GDF-3
Adult stem cells ability for proper tissue orginization, growth or repair rquire that there be restrictions on developmental potential of adult stem cells. These limits are
strictly imposed by powerful molecular restraints on gene expression and are heritable during many rounds of cell division
an example of how adult stem cells show relaxation of molecular restraints/restrictions on gene expression in an altered environment
Plasticity (note that plasticity is observed usually at low frequency)
Most work suggest that the application of adullt stem cells
is restricted in capacity and growth and is thus not a replacable alternative for embryonic stem cells.
Somatic Cell Nuclear transfer
- Combines cloning methods with embyronic stem cell technology to produce cells which are custom made for patient
-
Purpose
- a promising solution to problem of tissue rejection as cells express the patient’s genes
- Embryonic stem cell lines created from patients with certain diseases, to study disease development and to develop drugs
- Resuearch has enabled reprogramming of adult cells without going through embryo step
