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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4518-4527. Prepublished online as a Blood First Edition Paper on February 8, 2007; DOI 10.1182/blood-2006-10-054247. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-054247v1 109/10/4518    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mantel, C. Articles by Broxmeyer, H. E. Search for Related Content PubMed PubMed Citation Articles by Mantel, C. Articles by Broxmeyer, H. E. Related Collections Apoptosis Stem Cells in Hematology Hematopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability Charlie Mantel1, Ying Guo1, Man Ryul Lee4, Min-Kyoung Kim2, Myung-Kwan Han1, Hirohiko Shibayama3, Seiji Fukuda1, Mervin C. Yoder1, Louis M. Pelus1, Kye-Seong Kim4, and Hal E. Broxmeyer1 1 Department of Microbiology & Immunology and the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, IN; 2 Department of Medical Genetics, Hanyang University College of Medicine, Seoul, South Korea; 3 Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Japan; 4 Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul, South Korea Karyotypic abnormalities in cultured embryonic stem cells (ESCs), especially near-diploid aneuploidy, are potential obstacles to ESC use in regenerative medicine. Events causing chromosomal abnormalities in ESCs may be related to events in tumor cells causing chromosomal instability (CIN) in human disease. However, the underlying mechanisms are unknown. Using multiparametric permeabilized-cell flow cytometric analysis, we found that the mitotic-spindle checkpoint, which helps maintain chromosomal integrity during all cell divisions, functions in human and mouse ESCs, but does not initiate apoptosis as it does in somatic cells. This allows an unusual tolerance to polyploidy resulting from failed mitosis, which is common in rapidly proliferating cell populations and which is reduced to near-diploid aneuploidy, which is also common in human neoplastic disease. Checkpoint activation in ESC-derived early-differentiated cells results in robust apoptosis without polyploidy/aneuploidy similar to that in somatic cells. Thus, the spindle checkpoint is "uncoupled" from apoptosis in ESCs and is a likely source of karyotypic abnormalities. This natural behavior of ESCs to tolerate/survive varying degrees of ploidy change could complicate genome-reprogramming studies and stem-cell plasticity studies, but could also reveal clues about the mechanisms of CIN in human tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Guo, C. Mantel, R. A. Hromas, and H. E. Broxmeyer Oct-4 Is Critical for Survival/Antiapoptosis of Murine Embryonic Stem Cells Subjected to Stress: Effects Associated with Stat3/Survivin Stem Cells, January 1, 2008; 26(1): 30 - 34. [Abstract] [Full Text] [PDF]

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