biology Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...

and

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

, stem cell genomics is the analysis of the

genome 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 genes, other functional regions of the genome such as ...

s of

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

. 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.

Applications

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 ...

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

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

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 ...

sequencing and looking at the epigenetic changes of stem cells and subsequent products.

Single cell phenotypic analysis

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 (physical form and structure), its developmental processes, its biochemical and physiological propert ...

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.

Alzheimer's disease

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 and Kazutoshi Takahashi in Kyoto, Jap ...

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 neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

(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, Sox2, KLF4 and cMYC. 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.

Other diseases

This technique would be used for similar diseases, like

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(ALS) and spinal muscular atrophy (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.

Methods

Included in the study of stem cell genomics, is epigenomics, 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 cells (hESCs).

Bivalent domains

This includes investigation into bivalent domains as promoters or

chromatin Chromatin is a complex of DNA and protein found in eukaryote, 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 r ...

regions that are modified by transcriptional initiation 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 (genetics), transcription or Translation (biology), translation and is often used in res ...

Active enhancers

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 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 opposite react ...

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

H3- H3K27ac 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, down ...

Methylation

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 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.

Regulatory factors

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