Plzf is required in adult male germ cells for stem cell self-renewal.
F. William Buaas,Andrew L Kirsh,Manju Sharma,Derek J. McLean,Jamie L Morris,Michael D. Griswold,Dirk G. de Rooij,Robert E. Braun +7 more
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TLDR
It is shown that the classical mouse mutant luxoid contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and this is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.Abstract:
Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.read more
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MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline.
Michelle A. Carmell,Angélique Girard,Angélique Girard,Henk J. G. van de Kant,Déborah Bourc'his,Timothy H. Bestor,Dirk G. de Rooij,Gregory J. Hannon +7 more
TL;DR: The observations suggest a conserved function for Piwi-clade proteins in the control of transposons in the germline, and this work examines the effects of disrupting the gene encoding the third family member, MIWI2.
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Essential role of Plzf in maintenance of spermatogonial stem cells
Jose A. Costoya,Robin M. Hobbs,Maria Barna,Giorgio Cattoretti,Katia Manova,Meena Sukhwani,Kyle E. Orwig,Debra J. Wolgemuth,Pier Paolo Pandolfi +8 more
TL;DR: Results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool.
Journal ArticleDOI
p63 Is Essential for the Proliferative Potential of Stem Cells in Stratified Epithelia
TL;DR: P63, a gene whose deletion in mice results in the catastrophic loss of all stratified epithelia, is analyzed and it is demonstrated that p63 is strongly expressed in epithelial cells with high clonogenic and proliferative capacity and that stem cells lacking p63 undergo a premature proliferative rundown.
Journal ArticleDOI
Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage
Yechiel Elkabetz,Georgia Panagiotakos,George Al Shamy,Nicholas D. Socci,Viviane Tabar,Lorenz Studer +5 more
TL;DR: It is proposed that R-NSCs represent the first characterized NSC stage capable of responding to patterning cues that direct differentiation toward region-specific neuronal fates, and offer new tools for harnessing the differentiation potential of human ESCs.
Journal ArticleDOI
The Transcription Factor PLZF Directs the Effector Program of the NKT Cell Lineage
Adam K. Savage,Michael G. Constantinides,Jin Han,Damien Picard,Emmanuel Martin,Bofeng Li,Olivier Lantz,Albert Bendelac +7 more
TL;DR: PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development and is exquisitely specific to CD1d-restricted N KT cells and human MR1-specific MAIT cells.
References
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Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
TL;DR: A role is established for Oct-3/4 as a master regulator of pluripotency that controls lineage commitment and the sophistication of critical transcriptional regulators is illustrated and the consequent importance of quantitative analyses are illustrated.
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Formation of Pluripotent Stem Cells in the Mammalian Embryo Depends on the POU Transcription Factor Oct4
Jennifer Nichols,Branko Zevnik,Konstantinos Anastassiadis,Hitoshi Niwa,Daniela Klewe-Nebenius,Ian Chambers,Hans R. Schöler,Austin Smith +7 more
TL;DR: It is reported that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo and also determines paracrine growth factor signaling from stem cells to the trophectoderm.
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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
In-Kyung Park,Dalong Qian,Mark J. Kiel,Michael W. Becker,Michael Pihalja,Irving L. Weissman,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +8 more
TL;DR: The results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs, which are required for haematopoiesis to persist for the lifetime of the animal.
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Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells
Julie Lessard,Guy Sauvageau +1 more
TL;DR: Evidence is provided that the proliferative potential of leukaemic stem and progenitor cells lacking Bmi-1 is compromised because they eventually undergo proliferation arrest and show signs of differentiation and apoptosis, leading to transplant failure of the leukaemia.
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Role of the histone deacetylase complex in acute promyelocytic leukaemia
Richard J. Lin,Richard J. Lin,Richard J. Lin,Laszlo Nagy,Laszlo Nagy,Satoshi Inoue,Wenlin Shao,Wilson H. Miller,Ronald M. Evans,Ronald M. Evans +9 more
TL;DR: The findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease.