{"527571":{"#nid":"527571","#data":{"type":"news","title":"Cellular Choice: Liver or Pancreas?","body":[{"value":"\u003Cp class=\u0022p1\u0022\u003EMultipotent progenitor cells play a vital role in the development and regeneration of various types of mature tissues, including diseases like cancer. So it\u2019s important to understand the mechanisms of how they differentiate into some tissues and organs, but not others.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThat\u2019s what Chong Shin, researcher in the Petit Institute for Bioengineering and Bioscience, is working on. Recently published research from her lab explains how the common progenitors of the liver and the pancreas make that developmental choice \u2013 to become a liver or pancreas. Their findings will allow researchers to predict the development potential of a progenitor while enhancing stem cell differentiation into specific liver or pancreas lineages.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe liver and pancreas originate from a common multipotent source \u2013 hepatopancreatic progenitors. Previously during her postdoctoral training at the University of California at San Francisco, Shin showed that Bone morphogenetic protein 2b (Bmp2b) signaling is essential for determining which direction these progenitors will take \u2013 liver or pancreas.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cBut we didn\u2019t understand what is beneath the mechanism, how it\u2019s controlled. We didn\u2019t understand the details,\u201d says Shin, assistant professor in the School of Biology and the corresponding author of the paper, entitled, \u201cFour and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for \u03b2-Cell Regeneration,\u201d published recently in \u003Cem\u003EPLOS Genetics\u003C\/em\u003E.\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003EThrough transcriptome profiling of endodermal tissues exposed to increased or decreased Bmp2b signaling, the researchers discovered a zebrafish gene,\u0026nbsp;\u003Cem\u003Efour and a half LIM domains 1b\u003C\/em\u003E\u0026nbsp;(\u003Cem\u003Efhl1b\u003C\/em\u003E), as a novel target of Bmp2b signaling. Primarily expressed in the embryonic liver, \u003Cem\u003Efhl1b\u003C\/em\u003E generally suppresses specification of the pancreas and induces the liver.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003EThe researchers employed a form of fate mapping called single-cell lineage tracing to show that depletion of\u0026nbsp;\u003Cem\u003Efhl1b\u003C\/em\u003E\u0026nbsp;caused a liver-to-pancreas fate switch (i.e., liver development is suppressed and the pancreas is induced), while overexpression of \u003Cem\u003Efhl1b\u003C\/em\u003E redirected pancreatic progenitors to become liver cells.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003E\u201cWe were able to basically track a single progenitor cell and all of its progeny, so it\u2019s a very cool technique,\u201d says Jin Xu, a graduate student researcher in Shin\u2019s lab and the lead author of the paper. \u201cUsing this technique, we discovered that we can precisely tell what happens when we have more or less of this gene being expressed.\u201d\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003EAdditionally, they discovered that \u003Cem\u003Efhl1b\u003C\/em\u003E regulates regeneration of insulin-secreting beta cells. Loss of \u003Cem\u003Efhl1b\u003C\/em\u003E increased the regenerative capacity of beta cells by increasing \u003Cem\u003Epdx1\u003C\/em\u003E gene, which is essential for pancreatic development.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003ETaken altogether, the researchers\u2019 data reveals novel and critical functions of \u003Cem\u003Efhl1b\u003C\/em\u003E in the hepatic versus pancreatic fate decision and in beta cell regeneration. It\u2019s information that Shin says could lead to, \u201canother way of enhancing the development of healthy organs through directed differentiation,\u201d since effective Bmp suppression is critical for the induction of \u003Cem\u003EPDX1\u003C\/em\u003E and the subsequent generation of beta cells in human pluripotent stem cells (hESCs).\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EIn addition to Shin and Xu (based in the School of Biology), other authors of the research paper included two researchers from the Max Planck Institute for Polymer Research in Germany \u2013 Jiaxi Cui and Aranzazu Del Campo who synthesized the compound for the single-cell lineage tracing.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EShin credits Xu with carrying the biggest load, performing the experiments.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cI\u2019m so proud of him,\u201d Shin says. \u201cIt took 11 months from the initial submission to the final acceptance, and that included a lot of late nights, including plenty of all-nighters.\u201d\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p2\u0022\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003E\u003Cem\u003EThis research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK081351), the Regenerative Engineering and Medicine Research Center (2731336 and 1411318), the National Science Foundation (1354837), and the School of Biology (Georgia Institute of Technology).\u003C\/em\u003E\u003C\/p\u003E\u003Cp class=\u0022p3\u0022\u003E\u003Cstrong\u003ECitation: \u003C\/strong\u003EXu J, Cui J, Del Campo A, Shin CH (2016) Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for \u03b2-Cell Regeneration. \u003Cem\u003EPLoS Genet\u003C\/em\u003E 12(2): e1005831. doi:10.1371\/journal.pgen.1005831 (\u003Ca href=\u0022http:\/\/journals.plos.org\/plosgenetics\/article?id=10.1371\/journal.pgen.1005831\u0022\u003Ehttp:\/\/journals.plos.org\/plosgenetics\/article?id=10.1371\/journal.pgen.1005831\u003C\/a\u003E)\u003C\/p\u003E\u003Cp class=\u0022p2\u0022\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p2\u0022\u003E\u003Cstrong\u003ECONTACT:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p2\u0022\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Shin lab research focuses on understanding the signals that determine developmental fate"}],"field_summary":[{"value":"\u003Cp class=\u0022p1\u0022\u003EShin lab research focuses on understanding the signals that determine developmental fate\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Shin lab research focuses on understanding the signals that determine developmental fate"}],"uid":"28153","created_gmt":"2016-04-21 11:15:32","changed_gmt":"2016-10-08 03:21:25","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-04-21T00:00:00-04:00","iso_date":"2016-04-21T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"527561":{"id":"527561","type":"image","title":"insulin molecule","body":null,"created":"1461337200","gmt_created":"2016-04-22 15:00:00","changed":"1475895301","gmt_changed":"2016-10-08 02:55:01","alt":"insulin molecule","file":{"fid":"205609","name":"bigstock-insulin-molecules-118090541.jpg","image_path":"\/sites\/default\/files\/images\/bigstock-insulin-molecules-118090541_0.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/bigstock-insulin-molecules-118090541_0.jpg","mime":"image\/jpeg","size":1185393,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/bigstock-insulin-molecules-118090541_0.jpg?itok=YxhPfDGZ"}},"527551":{"id":"527551","type":"image","title":"Chong Shin and Jin Xu","body":null,"created":"1461337200","gmt_created":"2016-04-22 15:00:00","changed":"1475895301","gmt_changed":"2016-10-08 02:55:01","alt":"Chong Shin and Jin Xu","file":{"fid":"205608","name":"chong_and_jin.jpg","image_path":"\/sites\/default\/files\/images\/chong_and_jin_0.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/chong_and_jin_0.jpg","mime":"image\/jpeg","size":2156384,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/chong_and_jin_0.jpg?itok=mvHZq3w4"}}},"media_ids":["527561","527551"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"4407","name":"Graduate Student"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}