Stem Cells from Amniotic Fluid: Reprogrammed Amniotic Fluid Cells Can Generate All Types of Body Cells
ScienceDaily (Nov. 25, 2010) — Reprogrammed amniotic fluid cells can generate all types of body cells. High hopes rest on stem cells: one day, they may be used to treat many diseases. To date, embryos are the main source of these cells, but this raises ethical problems. Scientists at the Max Planck Institute for Molecular Genetics in Berlin have now managed to convert amniotic fluid cells into pluripotent stem cells. These amniotic fluid-derived iPS cells are hardly distinguishable from embryonic stem cells. However, they "remember" where they came from.
Top: Before their reprogramming into amniotic fluid iPS cells, human amniotic fluid cells are outwardly distinguishable from embryonic stem cells. Bottom left: Amniotic fluid iPS cells produce OCT4 (green), one of the most important marker proteins for embryonic stem cells. Bottom right: Starting from this embryonic stem cell phase, the amniotic fluid iPS cells can form hepatocyte-like cells and others. They produce the plasma protein alpha-fetoprotein (red), which is abundant in fetal liver. (Credit: Max Planck Institute for Molecular Genetics)
The research appears in the online journal PLoS ONE, published by the Public Library of Science.
The special abilities of embryonic stem cells can today be used in multiple "grown-up" cells (e.g. skin and hair cells). This is done by reprogramming the cells and converting them to "induced pluripotent stem cells" (iPS cells). These then possess the typical properties of embryonic stem cells, meaning they can generate any of the cell types of the human body (pluripotency), and they can multiply endlessly.
Stem cells with memory
The scientists have shown that the amniotic fluid iPS cells can form different human cell types. They have also discovered that induced pluripotent stem cells can remember the original cell type from which they were generated. During cellular reprogramming, various genes that control the development of stem cells are apparently switched on or remain active. This confirms other current research results, which show that iPS cells derived from distinct tissues are prone to follow their pre-destined developmental path upon spontaneous differentiation. "We don't know just yet whether this donor-cell type memory will have an impact on possible medical treatment, or which type of somatic cell-derived iPS cell will be most suitable for treatment," cautions Katharina Wolfrum of the Max Planck Institute for Molecular Genetics.
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The LARGE Principle of Cellular Reprogramming: Lost, Acquired and Retained Gene Expression in Foreskin and Amniotic Fluid-Derived Human iPS Cells
Katharina Wolfrum1,2, Ying Wang1, Alessandro Prigione1,Karl Sperling3, Hans Lehrach1, James Adjaye1,4*
1 Molecular Embryology and Aging Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, 2Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Berlin, Germany, 3 Institute of Human Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany, 4 Stem Cell Unit, Department of Anatomy, Medical College, King Saud University, Riyadh, Saudi Arabia
Abstract
Human amniotic fluid cells (AFCs) are routinely obtained for prenatal diagnostics procedures. Recently, it has been illustrated that these cells may also serve as a valuable model system to study developmental processes and for application in regenerative therapies. Cellular reprogramming is a means of assigning greater value to primary AFCs by inducing self-renewal and pluripotency and, thus, bypassing senescence. Here, we report the generation and characterization of human amniotic fluid-derived induced pluripotent stem cells (AFiPSCs) and demonstrate their ability to differentiate into the trophoblast lineage after stimulation with BMP2/BMP4. We further carried out comparative transcriptome analyses of primary human AFCs, AFiPSCs, fibroblast-derived iPSCs (FiPSCs) and embryonic stem cells (ESCs). This revealed that the expression of key senescence-associated genes are down-regulated upon the induction of pluripotency in primary AFCs (AFiPSCs). By defining distinct and overlapping gene expression patterns and deriving the LARGE (Lost, Acquired and Retained Gene Expression) Principle of Cellular Reprogramming, we could further highlight that AFiPSCs, FiPSCs and ESCs share a core self-renewal gene regulatory network driven by OCT4, SOX2 and NANOG. Nevertheless, these cell types are marked by distinct gene expression signatures. For example, expression of the transcription factors, SIX6, EGR2, PKNOX2, HOXD4, HOXD10, DLX5 and RAXL1, known to regulate developmental processes, are retained in AFiPSCs and FiPSCs. Surprisingly, expression of the self-renewal-associated gene PRDM14 or the developmental processes-regulating genes WNT3A and GSC are restricted to ESCs. Implications of this, with respect to the stability of the undifferentiated state and long-term differentiation potential of iPSCs, warrant further studies.
Citation: Wolfrum K, Wang Y, Prigione A, Sperling K, Lehrach H, et al. (2010) The LARGE Principle of Cellular Reprogramming: Lost, Acquired and Retained Gene Expression in Foreskin and Amniotic Fluid-Derived Human iPS Cells. PLoS ONE 5(10): e13703. doi:10.1371/journal.pone.0013703
Editor: Zhongjun Zhou, The University of Hong Kong, Hong Kong
Received: July 13, 2010; Accepted: October 6, 2010; Published: October 29, 2010
Copyright: © 2010 Wolfrum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors acknowledge support from the Bundesministerium für Bildung und Forschung (BMBF, Federal Ministry of Education and Research, www.bmbf.de; A.P.: 01GN0807; Y.W., J.A.: 0315398G) and the Max Planck Society (www.mpg.de). Contributions of K.W. were also made possible by funding from the Deutsche Forschungsgemeinschaft (DFG, www.dfg.de) through the Berlin-Brandenburg School for Regenerative Therapies (BSRT, www.bsrt.de) GSC 203. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: adjaye@molgen.mpg.de
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