Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells.

Abstract:

:Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we demonstrate the generation of iPSC lines from human pancreatic islet beta cells. These reprogrammed cells acquired markers of pluripotent cells and differentiated into the three embryonic germ layers. However, the beta cell-derived iPSCs (BiPSCs) maintained open chromatin structure at key beta-cell genes, together with a unique DNA methylation signature that distinguishes them from other PSCs. BiPSCs also demonstrated an increased ability to differentiate into insulin-producing cells both in vitro and in vivo, compared with ESCs and isogenic non-beta iPSCs. Our results suggest that the epigenetic memory may predispose BiPSCs to differentiate more readily into insulin producing cells. These findings demonstrate that HiPSC phenotype may be influenced by their cells of origin, and suggest that their skewed differentiation potential may be advantageous for cell replacement therapy.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Bar-Nur O,Russ HA,Efrat S,Benvenisty N

doi

10.1016/j.stem.2011.06.007

subject

Has Abstract

pub_date

2011-07-08 00:00:00

pages

17-23

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(11)00293-1

journal_volume

9

pub_type

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