Cellular trajectories and molecular mechanisms of iPSC reprogramming.

Abstract:

:The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallmarks and roadmaps of iPSC formation by describing relative kinetics of transcriptional, protein and epigenetic changes, including alterations in DNA methylation and histone modifications. Recently, technological advancements such as single-cell analyses, high-resolution genome-wide chromatin assays and more efficient reprogramming systems have been used to challenge and refine our understanding of the reprogramming process. Here, we will outline novel insights into the molecular mechanisms underlying iPSC formation, focusing on how the core reprogramming factors OCT4, KLF4, SOX2 and MYC (OKSM) drive changes in gene expression, chromatin state and 3D genome topology. In addition, we will discuss unexpected consequences of reprogramming factor expression in in vitro and in vivo systems that may point towards new applications of iPSC technology.

journal_name

Curr Opin Genet Dev

authors

Apostolou E,Stadtfeld M

doi

10.1016/j.gde.2018.06.002

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

77-85

eissn

0959-437X

issn

1879-0380

pii

S0959-437X(17)30126-0

journal_volume

52

pub_type

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