Stem cell genomics analyzes the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

s of

stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

. Currently, this field is rapidly expanding due to the dramatic decrease in the cost of sequencing genomes. The study of stem cell genomics has wide reaching implications in the study of stem cell biology and possible therapeutic usages of stem cells. Application of research in this field could lead to

drug discovery In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...

and information on diseases by the molecular characterization of the pluripotent stem cell through DNA and

transcriptome The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...

sequencing and looking at the epigenetic changes of stem cells and subsequent products. One step in that process is single cell phenotypic analysis, and the connection between the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

and

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

of specific stem cells. While current genomic screens are done with entire populations of cells, focusing in on a single stem cell will help determine specific signaling activity associated with varying degrees of stem cell differentiation and limit background due to heterogeneous populations. Single cell analysis of

induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...

s (iPSCs), or stem cells able to differentiate into many different cell types, is a suggested method for treating such diseases like

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

(AD). This includes for understanding the differences between sporadic AD and familial AD. By first taking a skin sample from the patient and are transformed by transducing cells using retroviruses to encode such stem cell genes as

Oct4 Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...

, Sox2, KLF4 and

cMYC ''Myc'' is a family of regulator genes and proto-oncogenes that Genetic code, code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (N-Myc, MYCN). ''c-myc'' (a ...

. This allows for skin cells to be reprogrammed into patient-specific stem cell lines. Taking genomic sequences of these individual cells would allow for patient-specific treatments and furthering understanding of AD disease models. This technique would be used for similar diseases, like

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(ALS) and

spinal muscular atrophy Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic ...

(SMA). These stem cells developed from a singular patient would also be able to be used to produce cells affected in the above-mentioned diseases. As mentioned, it will also lead to patient specific phenotypes of each disease. Further chemical analyses to develop safer drugs can be done through sequence information and cell-culture tests on iPSCs. After development on a specific drug, it can be transferred to other patient diseased cells while also being safety tested. Included in the study of stem cell genomics, is

epigenomics Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigen ...

, genomic-scale studies on chromatin regulatory variation. These studies also hope to expand research into regenerative medicine models and stem cell differentiation. Cell-type specific gene expression patterns during development occur as the result of interactions the chromatin level. Stem cell epigenomics focuses in on the epigenetic plasticity of

human embryonic stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s (hESCs). This includes investigation into bivalent domains as promoters or

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

regions that are modified by

transcriptional initiation Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...

and related to

gene silencing Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence gen ...

. They are also looking at the differences between active versus poised enhancers or enhancers that specifically control signaling-dependent gene regulation. Active enhancers are marked by

acetylation : In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

H3-

H3K27ac H3K27ac is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates acetylation of the lysine residue at N-terminal position 27 of the histone H3 protein. H3K27ac is associated with the higher activation o ...

and while poised are instead methylated at

H3K27me3 H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein. This tri-methylation is associated with the Downregulation and upregulation, dow ...

. Stem cell epigenomic studies are also looking into DNA methylation patterns, specifically characteristics of hydroxy methylation versus overall methylation and the difference between methylation of

CpG-island The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...

rich and CpG poor promoters. It has been found in mouse embryonic stem cells (mESC) that implanted mESC took up similar characteristics of histone methylation of the embryos where they transplanted into, indicating that methylation may be indicative of environment. This will guide studies into the differences between induced pluripotent and embryonic stem cells. These studies hope to produce information on iPSC differentiation capacity by first needing to enhance chromatin signature reading. It also hopes to produce to look into regulatory factors that control human embryonic development.Rada-Iglesias, A., & Wysocka, J. (2011). Epigenomics of human embryonic stem cells and induced pluripotent stem cells: insights into pluripotency and implications for disease, 1–13. Using drug therapy techniques as mentioned earlier, epigenomics would also allow for more information on drug activity.

References

{{DEFAULTSORT:Stem Cell Genomics Stem cells

See also

References