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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

Schematic showing the use of human pluripotent stem cells from patients with diabetes and metabolic diseases to study disease mechanisms in vitro. Human induced pluripotent stem cells (hiPSCs) derived from patients with monogenic diabetes, syndromes of insulin resistance, type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndromes can be differentiated into pancreatic cells, skeletal myocyotes, hepatic cells, adipocytes and immune cells, where relevant, to study disease mechanisms in vitro.
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fig2: Schematic showing the use of human pluripotent stem cells from patients with diabetes and metabolic diseases to study disease mechanisms in vitro. Human induced pluripotent stem cells (hiPSCs) derived from patients with monogenic diabetes, syndromes of insulin resistance, type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndromes can be differentiated into pancreatic cells, skeletal myocyotes, hepatic cells, adipocytes and immune cells, where relevant, to study disease mechanisms in vitro.

Mentions: In general, the strategy to carry out in vitro disease modeling of diabetes and related metabolic syndromes with hPSCs and genome editing tools would be to 1) derive hiPSCs from patients with these conditions, 2) generate “repaired/corrected” isogenic controls [53] and then 3) differentiate them into pancreatic cells or target cells of relevance, such as immune cells in the case of T1D or myocytes, adipocytes and hepatocytes in the case of T2D (Figure 2). If patient material is inaccessible, one could introduce (naturally occurring) mutations or gene variants into hESCs and differentiate them accordingly to study disease mechanisms. Since excellent reviews have been published recently, we will provide a brief overview to familiarize the reader with the classification of diabetes and metabolic disorders.


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

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

Schematic showing the use of human pluripotent stem cells from patients with diabetes and metabolic diseases to study disease mechanisms in vitro. Human induced pluripotent stem cells (hiPSCs) derived from patients with monogenic diabetes, syndromes of insulin resistance, type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndromes can be differentiated into pancreatic cells, skeletal myocyotes, hepatic cells, adipocytes and immune cells, where relevant, to study disease mechanisms in vitro.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

fig2: Schematic showing the use of human pluripotent stem cells from patients with diabetes and metabolic diseases to study disease mechanisms in vitro. Human induced pluripotent stem cells (hiPSCs) derived from patients with monogenic diabetes, syndromes of insulin resistance, type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndromes can be differentiated into pancreatic cells, skeletal myocyotes, hepatic cells, adipocytes and immune cells, where relevant, to study disease mechanisms in vitro.
Mentions: In general, the strategy to carry out in vitro disease modeling of diabetes and related metabolic syndromes with hPSCs and genome editing tools would be to 1) derive hiPSCs from patients with these conditions, 2) generate “repaired/corrected” isogenic controls [53] and then 3) differentiate them into pancreatic cells or target cells of relevance, such as immune cells in the case of T1D or myocytes, adipocytes and hepatocytes in the case of T2D (Figure 2). If patient material is inaccessible, one could introduce (naturally occurring) mutations or gene variants into hESCs and differentiate them accordingly to study disease mechanisms. Since excellent reviews have been published recently, we will provide a brief overview to familiarize the reader with the classification of diabetes and metabolic disorders.

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