scholarly journals The RNA binding protein Swm is critical for Drosophila melanogaster intestinal progenitor cell maintenance

2022 ◽  
Author(s):  
Ishara S Ariyapala ◽  
Kasun Buddika ◽  
Heather A Hundley ◽  
Brian Calvi ◽  
Nicholas Sokol

The regulation of stem cell survival, self-renewal, and differentiation is critical for the maintenance of tissue homeostasis. Although the involvement of signaling pathways and transcriptional control mechanisms in stem cell regulation have been extensively investigated, the role of post-transcriptional control is still poorly understood. Here we show that the nuclear activity of the RNA-binding protein Second Mitotic Wave Missing (Swm) is critical for Drosophila intestinal stem cells (ISCs) and their daughter cells, enteroblasts (EBs), to maintain their identity and function. Loss of swm in these intestinal progenitor cells leads ISCs and EBs to lose defined cell identities, fail to proliferate, and detach from the basement membrane, resulting in severe progenitor cell loss. swm loss further causes nuclear accumulation of poly(A)+ RNA in progenitor cells. Swm associates with transcripts involved in epithelial cell maintenance and adhesion, and the loss of swm, while not generally affecting the levels of these Swm-bound mRNAs, leads to elevated expression of proteins encoded by some of them, including the fly orthologs of Filamin and Talin. Taken together, this study indicates a role for Swm in adult stem cell maintenance, and raises the possibility that nuclear post-transcriptional gene regulation plays vital roles in controlling adult stem cell maintenance and function.

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Michalina Janiszewska ◽  
Mario-Luca Suva ◽  
Riekelt H. Houtkooper ◽  
Virginie Clement-Schatlo ◽  
Ivan Stamenkovic

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi227-vi227
Author(s):  
Tanwarat Sanvoranart ◽  
Leo Kim ◽  
Qiulian Wu ◽  
Xun Jin ◽  
Deobrat Dixit ◽  
...  

2016 ◽  
Vol 30 (22) ◽  
pp. 2459-2474 ◽  
Author(s):  
Nils Degrauwe ◽  
Mario-Luca Suvà ◽  
Michalina Janiszewska ◽  
Nicolo Riggi ◽  
Ivan Stamenkovic

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 228-229
Author(s):  
Barbara Anne Fraser ◽  
Alexander Sobinoff ◽  
Gary Hime ◽  
Nicole Siddall ◽  
Shaun Roman ◽  
...  

2009 ◽  
Vol 5 (1) ◽  
pp. 64-75 ◽  
Author(s):  
Xiaohua Su ◽  
Maryline Paris ◽  
Young Jin Gi ◽  
Kenneth Y. Tsai ◽  
Min Soon Cho ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2812-2822 ◽  
Author(s):  
Tao Wang ◽  
Vijayalakshmi Nandakumar ◽  
Xiao-Xia Jiang ◽  
Lindsey Jones ◽  
An-Gang Yang ◽  
...  

Key Points Mysm1 is required to maintain the quiescence and pool size of HSC, and its deletion severely impairs the survival and function of HSC. Mysm1 controls HSC homeostasis by regulating Gfi1 expression via modulating histone modifications and transcriptional factors recruitment.


PLoS Genetics ◽  
2019 ◽  
Vol 15 (6) ◽  
pp. e1008187 ◽  
Author(s):  
Benjamin Angulo ◽  
Shrividhya Srinivasan ◽  
Benjamin J. Bolival ◽  
Gonzalo H. Olivares ◽  
Allyson C. Spence ◽  
...  

2017 ◽  
Vol 91 (17) ◽  
Author(s):  
Dasol Han ◽  
Sung-Hyun Byun ◽  
Juwan Kim ◽  
Mookwang Kwon ◽  
Samuel J. Pleasure ◽  
...  

ABSTRACT Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells in vitro, indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after in utero electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2+ cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2+ callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis. IMPORTANCE HCMV brain pathogenesis has been studied in limited experimental settings, such as in vitro HCMV infection of neural progenitor cells or in vivo murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in the context of the embryonic brain using an in utero gene transfer tool. Surprisingly, IE2, but not HCMV IE1 or murine CMV ie3, interferes pleiotropically with key neurodevelopmental processes, including neural stem cell regulation, proper positioning of migrating neurons, and the callosal axon projections important for communication between the hemispheres. Our data suggest that the wide spectrum of clinical outcomes, ranging from mental retardation to microcephaly, caused by congenital HCMV infection can be sufficiently explained in terms of IE2 action alone.


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