Cell Cycle Regulators in Adult Stem Cells

Author(s):  
Tao Cheng ◽  
David T. Scadden
2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan Moore ◽  
Stephen Lyle

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Léonard Hérault ◽  
Mathilde Poplineau ◽  
Adrien Mazuel ◽  
Nadine Platet ◽  
Élisabeth Remy ◽  
...  

Abstract Background Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging, heterogeneity of HSCs changes, contributing to the deterioration of the immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale. Results Through the analysis of 15,000 young and aged transcriptomes, we identified 15 groups of HSCs revealing rare and new specific HSC abilities that change with age. The implantation of new trajectories complemented with the analysis of transcription factor activities pointed consecutive states of HSC differentiation that were delayed by aging and explained the bias in differentiation of older HSCs. Moreover, reassigning cell cycle phases for each HSC clearly highlighted an imbalance of the cell cycle regulators of very immature aged HSCs that may contribute to their accumulation in an undifferentiated state. Conclusions Our results establish a new reference map of HSC differentiation in young and aged mice and reveal a potential mechanism that delays the differentiation of aged HSCs and could promote the emergence of age-related hematologic diseases.


2003 ◽  
Vol 278 (30) ◽  
pp. 28067-28078 ◽  
Author(s):  
Carl A. Gregory ◽  
Harpreet Singh ◽  
Anthony S. Perry ◽  
Darwin J. Prockop

2005 ◽  
Vol 7 (2) ◽  
pp. 172-178 ◽  
Author(s):  
Carl R. Walkley ◽  
Matthew L. Fero ◽  
Wei-Ming Chien ◽  
Louise E. Purton ◽  
Grant A. McArthur

2015 ◽  
Vol 24 (16) ◽  
pp. 1888-1900 ◽  
Author(s):  
Nilay Yogeshkumar Thakar ◽  
Dmitry Alexander Ovchinnikov ◽  
Marcus Lachlan Hastie ◽  
Jeffrey Gorman ◽  
Ernst Jurgen Wolvetang

2013 ◽  
Vol 49 (5) ◽  
pp. 934-946 ◽  
Author(s):  
Philipp B. Staber ◽  
Pu Zhang ◽  
Min Ye ◽  
Robert S. Welner ◽  
César Nombela-Arrieta ◽  
...  

2018 ◽  
Author(s):  
Hardik P. Gala ◽  
Debarya Saha ◽  
Nisha Venugopal ◽  
Ajoy Aloysius ◽  
Jyotsna Dhawan

AbstractAdult stem cells persist in mammalian tissues by entering a state of reversible arrest or quiescence associated with low transcription. Using cultured myoblasts and primary muscle stem cells, we show that RNA synthesis is strongly repressed in G0, returning within minutes of activation. We investigate the underlying mechanism and reveal a role for promoter-proximal RNAPol II pausing: by mapping global Pol II occupancy using ChIP-seq, in conjunction with RNA-seq to identify repressed transcriptional networks unique to G0. Strikingly, Pol II pausing is enhanced in G0 on genes encoding regulators of RNA biogenesis (Ncl, Rps24, Ctdp1), and release of pausing is critical for cell cycle re-entry. Finally, we uncover a novel, unexpected repressive role of the super-elongation complex component Aff4 in G0-specific stalling. We propose a model wherein Pol II pausing restrains transcription to maintain G0, preconfigures gene networks required for the G0-G1 transition, and sets the timing of their transcriptional activation.


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