Advanced Molecular Genetics-Biology 566
Stem Cells - Expression Profiles
"The term stem cells is used to describe those cells that serve as a normal reservoir for new cells needed to replace damaged or dying cells. A fundamental characteristic of stem cells is the lasting ability to multiply when called upon. Stem cells have the ability to differentiate into specialized cells that can no longer divide." (Kiessling & Anderson, 2003)
Embryonic Stem Cells
"Before organs are formed, embryos of all species are comprised of a collection of cells with potential to give rise to many different organs and tissues. Such cells with plural potentiality are termed pluripotent stem cells. They divide endlessly in laboratory culture dishes and maintain the ability to differentiate into numerous types of cells when exposed to the appropriate growth factors." (Kiessling & Anderson, 2003)
Adult Stem Cells
"After their formation in the fetus, some tissues and organs continue to maintain a population of stem cells throughout childhood and into adulthood. Even though these cells appear early in development, they are called adult stem cells. One example is blood vessels that readily repair damage and can actually regenerate." (Kiessling & Anderson, 2003)
"Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells. (Ramalho-Santos et al., 2002)
"The three best characterized types of stem cells (SCs) in vertebrates are embryonic (ESC), neural (NSC), and hematopoietic (HSC). There is indirect evidence for SCs in intestive, skin, muscle, and liver, but their isolation has remained elusive."
Established transcriptional profiles for transcripts present in SC but not in differentiated cells. Comparisons were done as follows:
|Pluripotent Stem Cell||Adult Stem Cell||Differentiated Cells|
Embryonic Stem Cells
Neural Stem Cells
|Differentiated cells from lateral ventricles of the brain|
Hematopoietic Stem Cells
|Main cell population of the bone marrow.|
Transcription profiles were determined by hybridization of transcripts from each tissue type to replicates of Affymetrix U74Av2 microarray chips.
Recent studies have suggested that the potential of adult SCs may be broader that previously thought, suggesting that transcription levels of SCs may be similar.
These studies show that SCs are distinct in that each SC type can clarly be identified by highly expressed genes that are not enriched in other SCs.
The data show that there is a subset of 230 genes that are commonly enriched in all SCs.
A number of hybridization were to ESTs, Expressed Sequence Tags. ESTs are cloned from mRNA transcripts that are expressed in specific tissues and are used early in genome analysis to look at the coding potential of organisms. ESTs may or may not be mapped to genomic locations and therefore provide a potential for further investigation.
HSCs are more similar to the main cell population of the bone marrow than to any other sample.
NSCs are more similar to ESCs than to any other cell sample.
ESCs and NSCs are similar not only in enriched and depleted genes, but in the overall pattern of gene expression values.
The global overlap between gene expressed in ESCs and NSCs supports a "default model" for neural development. This model is based on results that show that embryonic cells of both frogs and mice become neural cells in the absence of cell-to-cell signaling.
There were 216 gene enriched and common to all three SCs. "These genes are likely to reveal core stem cell properties that underlie self-renewal and the ability to generate differentiated progeny." Propose that essential attributes of stemness include:
- Active JAK/STAT transducers and activators of transcription
- Active TGF-beta (transcription growth factor)
- Active Yes (Yamaguchi sarcoma) kinase
- Active Notch signaling
- Capacity to sense growth hormone and thrombin
- Interaction with the extracellular matrix via integrin alpha6/beta1, Adam9, and bystin
- Engagement in the cell cycle
- High resistance to stress with upregulated DNA repair, protein folding, ubiquitin system and detoxifier systems
-Remodeled chromatin acted upon by DNA helicases, DNA methylases, and histone deacetylases
- Translation regulated by RNA helicases of the Vasa type.
"One theme emerging from these data is that SCs have characteristics of cells under stress."
"Of the 216 genes enriched in all three SCs, only 60 have been mapped to a chromosomal location. Twoeve of these genes are on chromosome 17, which means that this chromosome contains 3.7 times the number of SC-enriched genes that would be present if these genes were randomly distributed."
"The t-complex on chromosome 17 contains genes involved in embryonic development and spermatogenesis, and founr SC-enriched genes map in the t-complex. It is possible that some of the clustered SC-enriched genes are coregulated at a local chromatin level."
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