Single-cell Expression Analyses During Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Sep 18

PMID 22980981

Citations 466

Authors

Yosef Buganim

Dina A Faddah

Albert W Cheng

Elena Itskovich

Styliani Markoulaki

Kibibi Ganz

Sandy L Klemm

Alexander van Oudenaarden

Rudolf Jaenisch

Affiliations

Soon will be listed here.

Abstract

During cellular reprogramming, only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene expression technologies to profile 48 genes in single cells at various stages during the reprogramming process. Analysis of early stages revealed considerable variation in gene expression between cells in contrast to late stages. Expression of Esrrb, Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs than expression of the previously suggested reprogramming markers Fbxo15, Fgf4, and Oct4. Stochastic gene expression early in reprogramming is followed by a late hierarchical phase with Sox2 being the upstream factor in a gene expression hierarchy. Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency circuitry.

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