Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues
| Autor: | Jason Sinclair, Jennifer Idol, Haigen Huang, Blake Carrington, Gaurav K. Varshney, Sunny C. Huang, MaryPat Jones, Alberto Rissone, Raman Sood, Shawn M. Burgess, Lisha Xu, Erin Jimenez, Claire Slevin, Kade P Pettie, Wuhong Pei, Kevin Bishop, Shuo Lin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
1.1 Normal biological development and functioning Biomedical Engineering Medicine (miscellaneous) Mutagenesis (molecular biology technique) lcsh:Medicine Biology Gene mutation Regenerative Medicine Regenerative medicine Article 03 medical and health sciences Underpinning research otorhinolaryngologic diseases medicine Genetics 2.1 Biological and endogenous factors Aetiology Zebrafish Gene integumentary system 5.2 Cellular and gene therapies Regeneration (biology) lcsh:R Human Genome Neurosciences Ear Cell Biology biology.organism_classification 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure sense organs Hair cell Development of treatments and therapeutic interventions Developmental Biology Genetic screen Biotechnology |
| Zdroj: | NPJ Regenerative medicine, vol 3, iss 1 npj Regenerative Medicine, Vol 3, Iss 1, Pp 1-11 (2018) NPJ Regenerative Medicine |
| Popis: | Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration. Identifying regenerative genes in non-mammalian vertebrates A study on zebrafish has genetically screened 254 genes and identified 7 genes implicated in the development and regeneration of hair cells and other tissues. Humans and other mammals cannot regrow hair cells—inner-ear sensory receptors that enable hearing—whereas non-mammalian vertebrates, including zebrafish, can regrow these following injury. Researchers from the United States, led by the National Institutes of Health’s Shawn Burgess, screened adult zebrafish for genes active during the regeneration of inner-ear epithelium. The researchers then produced zebrafish without these genes to study their functions. The studies tested 254 genes known to respond during regeneration, and identified seven specifically impacting regeneration. Most of these seven genes also functioned in liver and fin tissue regeneration. Understanding the mechanisms of these genes may enable future research into regenerative therapies in humans. |
| Databáze: | OpenAIRE |
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