PMID- 19935716 OWN - NLM STAT- MEDLINE DCOM- 20100312 LR - 20211203 IS - 1476-5594 (Electronic) IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 29 IP - 7 DP - 2010 Feb 18 TI - Embryoid body formation of human amniotic fluid stem cells depends on mTOR. PG - 966-77 LID - 10.1038/onc.2009.405 [doi] AB - Human amniotic fluid stem cells (hAFSCs) harbor high proliferative capacity and high differentiation potential and do not raise the ethical concerns associated with human embryonic stem cells. The formation of three-dimensional aggregates known as embryoid bodies (EBs) is the principal step in the differentiation of pluripotent embryonic stem cells. Using c-Kit-positive hAFSC lines, we show here that these stem cells harbor the potential to form EBs. As part of the two kinase complexes, mTORC1 and mTORC2, mammalian target of rapamycin (mTOR) is the key component of an important signaling pathway, which is involved in the regulation of cell proliferation, growth, tumor development and differentiation. Blocking intracellular mTOR activity through the inhibitor rapamycin or through specific small interfering RNA approaches revealed hAFSC EB formation to depend on mTORC1 and mTORC2. These findings demonstrate hAFSCs to be a new and powerful biological system to recapitulate the three-dimensional and tissue level contexts of in vivo development and identify the mTOR pathway to be essential for this process. FAU - Valli, A AU - Valli A AD - Department of Medical Genetics, Medical University of Vienna, Vienna, Austria. FAU - Rosner, M AU - Rosner M FAU - Fuchs, C AU - Fuchs C FAU - Siegel, N AU - Siegel N FAU - Bishop, C E AU - Bishop CE FAU - Dolznig, H AU - Dolznig H FAU - Madel, U AU - Madel U FAU - Feichtinger, W AU - Feichtinger W FAU - Atala, A AU - Atala A FAU - Hengstschlager, M AU - Hengstschlager M LA - eng GR - R01 HD060097/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091123 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (CRTC2 protein, human) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Multiprotein Complexes) RN - 0 (Proteins) RN - 0 (Transcription Factors) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Amniotic Fluid/*cytology MH - Animals MH - Cell Aggregation MH - Cell Line MH - Humans MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Mechanistic Target of Rapamycin Complex 1 MH - Multiprotein Complexes MH - Protein Serine-Threonine Kinases/*metabolism MH - Proteins MH - Stem Cells/*cytology/*metabolism MH - TOR Serine-Threonine Kinases MH - Transcription Factors/metabolism PMC - PMC8330845 MID - NIHMS511193 COIS- Conflict of interest The authors declare no conflict of interest. EDAT- 2009/11/26 06:00 MHDA- 2010/03/13 06:00 PMCR- 2021/08/03 CRDT- 2009/11/26 06:00 PHST- 2009/11/26 06:00 [entrez] PHST- 2009/11/26 06:00 [pubmed] PHST- 2010/03/13 06:00 [medline] PHST- 2021/08/03 00:00 [pmc-release] AID - onc2009405 [pii] AID - 10.1038/onc.2009.405 [doi] PST - ppublish SO - Oncogene. 2010 Feb 18;29(7):966-77. doi: 10.1038/onc.2009.405. Epub 2009 Nov 23.