Human embryonic stem cells as an in vitro model for studying developmental origins of type 2 diabetes

Table 1 The use of pluripotent stem cells as in vitro models for studying the developmental origins of health and diseases

Environmental insult(s)	Type of pluripotent stem cells	Cell lineage	Effects on differentiation	Ref.
Hyperglycemia (25-50 mmol/L)	hESC	Pancreatic	(1) Inhibited differentiation into DE; and (2) retained repressive H3K27me3 mark on DE marker promoters	[85]
Hyperglycemia (25-50 mmol/L)	mESC	Pancreatic	Inhibited differentiation into DE	[85]
TCDD (10 pmol/L)	hESC	Pancreatic	Dysregulated DNA methylome of genes related to diabetes	[99]
TCDD (10-100 pmol/L)	hESC	Pancreatic	(1) Dysregulated DNA methylome of genes related to insulin signaling and diabetes; (2) inhibited differentiation into pancreatic progenitor; and (3) promoted DNA hypermethylation of PRKAG1	[100]
Hyperglycemia (10 mmol/L), endothelin-1 (ET-1) (10 nmol/L), and cortisol (1 μmol/L)	hiPSC	Cardiac	(1) Inhibited cardiomyocyte differentiation; and (2) elevated oxidative stress in cardiomyocytes formed	[114]
Hyperglycemia (25 mmol/L)	mESC	Cardiac	Inhibited mesoderm and subsequent cardiomyocyte differentiation	[117]
Hyperglycemia (25 mmol/L)	mESC	Cardiac	Enhanced cardiomyocyte differentiation	[118]
TCDD (1 nmol/L)	mESC	Cardiac	Inhibited cardiomyocyte differentiation	[136]
TCDD (10-100 pmol/L)	hESC	Cardiac	Dysregulated DNA methylome of genes related to cardiomyopathy	[100]
BPA (1-8 μg/mL); PFOS (5-40 μg/mL); PFOA (10-80 μg/mL)	mESC	Cardiac	Inhibited cardiomyocyte differentiation	[137]
Hyperglycemia (25 mmol/L)	mESC	Neural	Inhibited neural differentiation	[125]

hESC: Human embryonic stem cells; TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin; DE: Definitive endoderm; BPA: Bisphenol A.