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Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools.

Teo AK, Gupta MK, Doria A, Kulkarni RN - Mol Metab (2015)

Bottom Line: Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling.We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases. hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes.The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02215, USA ; Discovery Research Division, Institute of Molecular and Cell Biology, Proteos, Singapore 138673, Singapore ; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

ABSTRACT

Background: Diabetes and metabolic syndromes are chronic, devastating diseases with increasing prevalence. Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling. With recent rapid advances in genome editing tools, these cells can now be genetically manipulated with relative ease to study how genes and gene variants contribute to diabetes and metabolic syndromes.

Scope of review: We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases.

Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

No MeSH data available.


Related in: MedlinePlus

Genome editing methodologies which can be applied to human pluripotent stem cells. Homologous recombination (HR), or the more advanced tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system can be applied to human pluripotent stem cells (hPSCs) either to 1) create naturally occurring mutations or 2) repair a mutation to generate isogenic controls in hPSCs, to understand the function of a gene of interest.
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fig1: Genome editing methodologies which can be applied to human pluripotent stem cells. Homologous recombination (HR), or the more advanced tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system can be applied to human pluripotent stem cells (hPSCs) either to 1) create naturally occurring mutations or 2) repair a mutation to generate isogenic controls in hPSCs, to understand the function of a gene of interest.

Mentions: Homologous recombination (HR), or gene targeting, is a method for introducing a particular DNA sequence into a host genome (Figure 1) [17]. When DNA double-strand breaks (DSBs) occur in cells (e.g. due to DNA damage), the DNA can be repaired either via HR or via (error-prone) non-homologous end joining (NHEJ) [18]. DNA repair by HR occurs either via the double-strand break repair (DSBR) pathway or the synthesis-dependent strand annealing (SDSA) pathway. The former commonly results in an exchange of nucleotide sequence(s) between the two strands of DNA (crossover), leading to genetic recombination in contrast to the SDSA pathway, which does not result in a crossover. The natural process of DNA damage and DSBR pathway is the conventional gene targeting method to insert transgenes into the genome without the use of nucleases (ZFNs, TALENs or CRISPR/Cas).


Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools.

Teo AK, Gupta MK, Doria A, Kulkarni RN - Mol Metab (2015)

Genome editing methodologies which can be applied to human pluripotent stem cells. Homologous recombination (HR), or the more advanced tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system can be applied to human pluripotent stem cells (hPSCs) either to 1) create naturally occurring mutations or 2) repair a mutation to generate isogenic controls in hPSCs, to understand the function of a gene of interest.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563028&req=5

fig1: Genome editing methodologies which can be applied to human pluripotent stem cells. Homologous recombination (HR), or the more advanced tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) or clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system can be applied to human pluripotent stem cells (hPSCs) either to 1) create naturally occurring mutations or 2) repair a mutation to generate isogenic controls in hPSCs, to understand the function of a gene of interest.
Mentions: Homologous recombination (HR), or gene targeting, is a method for introducing a particular DNA sequence into a host genome (Figure 1) [17]. When DNA double-strand breaks (DSBs) occur in cells (e.g. due to DNA damage), the DNA can be repaired either via HR or via (error-prone) non-homologous end joining (NHEJ) [18]. DNA repair by HR occurs either via the double-strand break repair (DSBR) pathway or the synthesis-dependent strand annealing (SDSA) pathway. The former commonly results in an exchange of nucleotide sequence(s) between the two strands of DNA (crossover), leading to genetic recombination in contrast to the SDSA pathway, which does not result in a crossover. The natural process of DNA damage and DSBR pathway is the conventional gene targeting method to insert transgenes into the genome without the use of nucleases (ZFNs, TALENs or CRISPR/Cas).

Bottom Line: Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling.We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases. hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes.The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02215, USA ; Discovery Research Division, Institute of Molecular and Cell Biology, Proteos, Singapore 138673, Singapore ; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

ABSTRACT

Background: Diabetes and metabolic syndromes are chronic, devastating diseases with increasing prevalence. Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling. With recent rapid advances in genome editing tools, these cells can now be genetically manipulated with relative ease to study how genes and gene variants contribute to diabetes and metabolic syndromes.

Scope of review: We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases.

Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

No MeSH data available.


Related in: MedlinePlus