{"id":10861,"date":"2016-12-12T07:55:27","date_gmt":"2016-12-12T07:55:27","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=10861"},"modified":"2016-12-12T07:55:27","modified_gmt":"2016-12-12T07:55:27","slug":"designer-switches-cell-fate-streamline-stem-cell-biology","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/designer-switches-cell-fate-streamline-stem-cell-biology\/","title":{"rendered":"Designer switches of cell fate could streamline stem cell biology"},"content":{"rendered":"
\"Micrograph
Micrograph of induced pluripotent stem cells generated from artificial transcription factors. The cells express green fluorescent protein after a key gene known as Oct4 is activated. ASUKA EGUCHI\/UW-MADISON<\/figcaption><\/figure>\n

Researchers at the University of Wisconsin\u2013Madison have developed a novel strategy to reprogram cells from one type to another in a more efficient and less biased manner than previous methods.<\/span><\/p>\n

The ability to convert cells from one type to another holds great promise for engineering cells and tissues for therapeutic application, and the new Wisconsin study could help speed research and bring the technology to the clinic faster.<\/span><\/p>\n

The new approach, published this week (Dec. 5, 2016) in the Proceedings of the National Academy of Sciences<\/em><\/a> (PNAS), uses a library of artificial transcription factors to switch on genes that convert cells from one type to another. Natural transcription factors are cellular molecules that bind to DNA to turn genes on and off. They help determine cell fate, meaning that if a cell is destined to be a skin cell, a heart cell or an eye cell, different transcription factors switch on specific sets of genes that program the cell to attain one state or another. Using artificial transcription factors made in the lab, researchers are trying to find which ones best mimic these natural changes in cell fate.<\/span><\/p>\n

\"Asuka
Asuka Eguchi<\/figcaption><\/figure>\n

\u201cOur interest in changing cell fate comes from understanding how cells selectively use the information in our genomes to make specific cell types and also from the many therapeutic benefits such knowledge can offer,\u201d says Asuka Eguchi, the study\u2019s lead author and a member of Professor Aseem Ansari<\/a>\u2019s lab in the UW\u2013Madison Department of Biochemistry<\/a>. \u201cFor example, if a patient needs a certain cell type, the idea is we can reprogram their own cells to what they need, rather than relying on donor cells. This allows us to study patient-specific cells and potentially avoids issues with immune response where a patient\u2019s body could reject the cells.\u201d<\/span><\/p>\n

Conventional methods for finding the correct factors to change cell fate require scientists to perform a trial-and-error approach. They need prior knowledge about which combination of the thousands of natural factors would possibly work within a tightly choreographed timeframe to program cell fate. It is a slow, laborious, failure-prone process, the researchers say. The new method utilizes \u201clibraries\u201d of millions of artificial transcription factors that were designed to bypass natural controls and switch on genes that might be activated in a given cell type. In addition, the factors contain an attachment that lets them bind and work in concert to affect genes, a step not traditionally taken.<\/span><\/p>\n

By exposing the library of factors to cells, they can see if cell fate changed in any of them. If so, they can revisit those cells to see which factors were responsible. For their experiments, the Wisconsin group started with mice fibroblasts, a cell in connective tissue, and looked for them to be reprogrammed into what are called induced pluripotent stem cells. Given proper cues, these types of stem cells can become any type of cell in an animal\u2019s body. The technique could also be applied to humans. By reprogramming, the researchers mean that the artificial factors would trigger all of the right genes to cause the cell to shift from one type to another.<\/span><\/p>\n

\u201cImagine you have millions of keys and only a unique key or combination of keys can turn a motor on,\u201d says Ansari, who is also affiliated with UW\u2013Madison\u2019s Genome Center of Wisconsin<\/a>. \u201cWe test all those keys in parallel and when we see the motor fire up, we go back to see exactly which key switched it on.\u201d<\/span><\/p>\n

In the process of testing their tool, the researchers discovered three combinations of the artificial factors that reprogrammed a fibroblast into a stem cell. The factors played a role similar to that of a natural transcription factor important in a process, called Oct4.<\/em><\/span><\/p>\n

\u201cIn this unbiased approach, we can try to basically cast a wide net on the whole genome and let the cell tell us if there are important genes perturbed,\u201d Ansari says. \u201cIt\u2019s a way to induce cell fate conversions without having to know what genes might be important because we are able to test so many by using an unbiased library of molecules that can search nearly every corner of the genome.\u201d<\/span><\/p>\n

The reprogramming of fibroblasts into stem cells has been well studied. The researchers put their approach to the test in this context because it places a high bar and requires significant changes to the cell. With this proof of concept, the Wisconsin scientists hope other researchers use their method to discover new genes that can drive more difficult conversions of cell fate.<\/span><\/p>\n

\u201cGenerating these pluripotent stem cells also helps us avoid having to make embryonic stem cells, which can be controversial,\u201d says Eguchi, who is a recent graduate of the UW\u2013Madison Cellular and Molecular Biology Training Program<\/a>. \u201cWe can also start better investigating direct conversions, which are conversions from one cell type to another without the need to go to the pluripotent stage first because that can cause problems in some contexts. This tool opens up the doors to research these areas more effectively.\u201d<\/span><\/p>\n

The W.M. Keck Foundation provided funding for the study, as did the National Institutes of Health\u2019s Progenitor Cell Biology Consortium. The NIH consortium brought together leading researchers from different scientific disciplines across campus as well as from the University of Minnesota and across the country.<\/span><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

The ability to convert cells from one type to another holds great promise for engineering cells and tissues for therapeutic application, and the new Wisconsin study could help speed research and bring the technology to the clinic faster.<\/p>\n","protected":false},"author":6,"featured_media":10862,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16,17],"tags":[],"class_list":["post-10861","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-biology","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500-150x150.png",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500-300x300.png",300,300,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",490,490,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",360,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",65,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",500,500,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",96,96,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/12\/ATF_iPS_cells-500x500.png",150,150,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Biology<\/a> Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10861","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=10861"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10861\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/10862"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=10861"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=10861"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=10861"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}