Meta-analysis of gene expression in human pancreatic islets after in vitro expansion.
Pancreatic islet transplantation as a potential cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta-cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional beta-cells remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and for which redifferentiation was attempted. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at redifferentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increase our understanding of the active pathways in expanded and redifferentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta-cell mass in T1D patients.
Kutlu
B
B
Institute for Systems Biology, Seattle, Washington, USA. bkutlu@systemsbiology.org
Kayali
A G
AG
Jung
S
S
Parnaud
G
G
Baxter
D
D
Glusman
G
G
Goodman
N
N
Behie
L A
LA
Hayek
A
A
Hood
L
L
D000328:Adult; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding