Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase
| Autor: | Sandy Klemm, Kibibi Ganz, Yosef Buganim, Elena Itskovich, Alexander van Oudenaarden, Styliani Markoulaki, Dina A. Faddah, Albert W. Cheng, Rudolf Jaenisch |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2012 |
| Předmět: |
Genetic Markers
Homeobox protein NANOG Induced Pluripotent Stem Cells Biology LIN28 Article General Biochemistry Genetics and Molecular Biology Cell Line Kruppel-Like Factor 4 Mice 03 medical and health sciences 0302 clinical medicine SOX2 Gene expression Animals Induced pluripotent stem cell Embryonic Stem Cells 030304 developmental biology Genetics 0303 health sciences Biochemistry Genetics and Molecular Biology(all) SOXB1 Transcription Factors Fibroblasts Microfluidic Analytical Techniques Cellular Reprogramming Embryo Mammalian Embryonic stem cell Cell biology KLF4 embryonic structures Single-Cell Analysis Transcriptome Reprogramming 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Cell, 150(6), 1209-1222. Elsevier B.V. |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2012.08.023 |
| Popis: | SummaryDuring 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. |
| Databáze: | OpenAIRE |
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