Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration

Author(s):  
Litao Tao ◽  
Haoze V. Yu ◽  
Juan Llamas ◽  
Talon Trecek ◽  
Xizi Wang ◽  
...  



2016 ◽  
Vol 40 ◽  
pp. 32-40 ◽  
Author(s):  
Jonathan S Kniss ◽  
Linjia Jiang ◽  
Tatjana Piotrowski


2014 ◽  
Vol 243 (10) ◽  
pp. 1187-1202 ◽  
Author(s):  
Mark E Lush ◽  
Tatjana Piotrowski


2019 ◽  
Vol 35 (1) ◽  
pp. 567-589 ◽  
Author(s):  
Nicolas Denans ◽  
Sungmin Baek ◽  
Tatjana Piotrowski

Deafness or hearing deficits are debilitating conditions. They are often caused by loss of sensory hair cells or defects in their function. In contrast to mammals, nonmammalian vertebrates robustly regenerate hair cells after injury. Studying the molecular and cellular basis of nonmammalian vertebrate hair cell regeneration provides valuable insights into developing cures for human deafness. In this review, we discuss the current literature on hair cell regeneration in the context of other models for sensory cell regeneration, such as the retina and the olfactory epithelium. This comparison reveals commonalities with, as well as differences between, the different regenerating systems, which begin to define a cellular and molecular blueprint of regeneration. In addition, we propose how new technical advances can address outstanding questions in the field.



2021 ◽  
Author(s):  
Sungmin Baek ◽  
Nhung T. T. Tran ◽  
Daniel C. Diaz ◽  
Ya-Yin Tsai ◽  
Tatjana Piotrowski

Loss of sensory hair cells in the mammalian inner ear leads to permanent hearing and vestibular defects, whereas loss of hair cells in zebrafish results in their regeneration. We used scRNA-Seq to characterize the transcriptional dynamics of hair cell regeneration in zebrafish at unprecedented spatio-temporal resolution. We uncovered three, sequentially activated modules. First, an injury/inflammatory response and downregulation of progenitor/stem cell maintenance genes within minutes after hair cell loss. Second, the transient activation of regeneration-specific genes. And third, a robust reactivation of developmental gene programs, including hair cell specification, cell cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are not only relevant for our understanding of hair cell regeneration and how we might be able to trigger it in mammals but also for regenerative processes in general. The data is searchable and publicly accessible via a web-based interface.



2019 ◽  
Author(s):  
Alberto Rissone ◽  
Erin Jimenez ◽  
Kevin Bishop ◽  
Blake Carrington ◽  
Claire Slevin ◽  
...  

AbstractMutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die a few weeks after birth. The only available therapeutic option for RD is bone marrow transplantation. To gain insight into the pathophysiology of RD, we previously created zebrafish models for an AK2 deficiency. One of the clinical features of RD is hearing loss, but its pathology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several non-mammalian vertebrates, including zebrafish. Therefore, we use our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a supportive therapeutic modality for RD patients, not only to increase their chances of survival, but to prevent or ameliorate their sensorineural hearing deficits.



2018 ◽  
Author(s):  
Mark E. Lush ◽  
Daniel C. Diaz ◽  
Nina Koenecke ◽  
Sungmin Baek ◽  
Helena Boldt ◽  
...  

AbstractLoss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized, proliferating support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to cycling hair cell progenitors and differentiated hair cells. We used single cell RNA-Sequencing (scRNA-Seq) of lateral line sensory organs and uncovered five different support cell types, including quiescent and activated stem cells. In silico ordering of support cells along a developmental trajectory identified cells that self-renew and new groups of genes required for hair cell differentiation. scRNA-Seq analyses of fgf3 mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. As a resource, we implemented a shiny application that allows the community to interrogate cell type specific expression of genes of interest.



2007 ◽  
Vol 34 (Fall) ◽  
pp. 134-144 ◽  
Author(s):  
Anna Kharlamova ◽  
Nancy L. Aarts


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