Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures.

Abstract:

:Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular origins, and this may bias subsequent differentiation. Neurons are difficult to reprogram, and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes. Here, we compare reprogramming efficiency of five different retinal cell types at two different stages of development. Retinal differentiation from each iPSC line was measured using a quantitative standardized scoring system called STEM-RET and compared to the epigenetic memory. Neurons with the lowest reprogramming efficiency produced iPSC lines with the best retinal differentiation and were more likely to retain epigenetic memory of their cellular origins. In addition, we identified biomarkers of iPSCs that are predictive of retinal differentiation.

journal_name

Cell Rep

journal_title

Cell reports

authors

Wang L,Hiler D,Xu B,AlDiri I,Chen X,Zhou X,Griffiths L,Valentine M,Shirinifard A,Sablauer A,Thiagarajan S,Barabas ME,Zhang J,Johnson D,Frase S,Dyer MA

doi

10.1016/j.celrep.2018.01.075

subject

Has Abstract

pub_date

2018-03-06 00:00:00

pages

2601-2614

issue

10

issn

2211-1247

pii

S2211-1247(18)30139-6

journal_volume

22

pub_type

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