{"id":2154,"date":"2018-02-16T18:27:18","date_gmt":"2018-02-17T02:27:18","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/never-accept-a-kidney-donation-from-a-mouse\/"},"modified":"2023-11-26T08:22:59","modified_gmt":"2023-11-26T16:22:59","slug":"never-accept-a-kidney-donation-from-a-mouse","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/never-accept-a-kidney-donation-from-a-mouse\/","title":{"rendered":"Never accept a kidney donation from a mouse"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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\n\n \n Press Release<\/span>\n\n\n\n<\/div>\n \n \n
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Never accept a kidney donation from a mouse<\/h1>\n\n\n<\/div>\n \n \n
\n \n February 16, 2018<\/span>\n <\/div>\n \n \n
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At an early stage, a nephron forming in the human kidney generates an S-shaped structure. Green cells will generate the kidneys\u2019 filtering device, and blue and red cells specialized regions responsible for distinct nephron activities. (Image courtesy of Stacy Moroz and Tracy Tran\/McMahon Lab)<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\r\n\r\n\n\n \n \n\n\n\n\n\n\n\n
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Researchers are hard at work building mini-kidneys from human cells\u2014using blueprints mostly drawn from lab mice. But mouse kidneys differ from their human counterparts in more than mere scale, as detailed by the USC Stem Cell\u00a0laboratory of Andy McMahon<\/a>\u00a0in three studies in the\u00a0Journal of the American Society of Nephrology<\/em>.
\n<\/span>\u201cIn mice, the kidney develops over a period of approximately two weeks, resulting in the formation of 16,000 filtration units called nephrons,\u201d said first author Nils Lindstrom. \u201cIn humans, this organ forms over a period of approximately 32 weeks, during which one million nephrons form. While mouse and human nephrons show some similar patterns of development, it\u2019s not entirely surprising that we also observe some major differences between these species.\u201d
\nOn the macro level, there are developmental differences in scale, timing and basic structure. For example, the human kidney possesses lobes, which the mouse kidney lacks.<\/p>\n

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\nOn the micro level, developing human kidneys also feature a greater diversity of cell types, and major differences in stem cell-like progenitors that build much of the kidney: nephron progenitors that generate functional nephron units, and interstitial progenitors that give rise to a variety of cells that connect the tubular networks of the kidney.
\nLindstrom and his colleagues also noted differences in the activity of what are known as \u201canchor genes,\u201d which scientists use as points of reference to determine the identity of various cell types. For example, in the developing mouse kidney, interstitial progenitors can be identified on the basis of high activity of a gene called\u00a0FoxD1<\/em>. Surprisingly, in the developing human kidney, both interstitial cells and nephron progenitors have high\u00a0FOXD1<\/em>\u00a0activity. Therefore, scientists relying on\u00a0FOXD1\u00a0<\/em>as an anchor gene will likely misidentify the cell types in developing human kidneys. Further, given the regulatory actions of\u00a0FOXD1<\/em>, and other genes that show similar behavior, the findings raise important questions about the different states of mouse and human nephron-forming progenitors.
\n\u201cOnly three out of 26 anchor genes conserve mouse-like activity in the human kidney,\u201d said Lindstrom. \u201cFurthermore, some of these anchor genes are implicated in kidney diseases, including cancer, that affect humans. So attempts to replicate mouse-like gene activity in human cells could have unintended consequences.\u201d
\nThe researchers chronicled several other similarities and differences in how this exquisitely complex organ develops in mice and humans. The three studies are: \u201cConserved and divergent features of human and mouse kidney organogenesis<\/a>,\u201d \u201cConserved and divergent molecular and anatomic features of human and mouse nephron patterning<\/a>,\u201d and \u201cConserved and divergent features of mesenchymal progenitor cell types within the cortical nephrogenic niche of the human and mouse kidney<\/a>.\u201d
\nIn another McMahon Lab study published in\u00a0PLoS Genetics<\/em>, postdoctoral fellow Lori O\u2019Brien, graduate student Qiuyu Guo and their colleagues focused on mouse kidney development. They identified regions of the genome, conserved between mouse and man, that regulate the genes that control nephron progenitor cells during kidney development. Much of human disease is thought to reside in changes in this regulatory component of the mammalian genome.<\/p>\n

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\"A
A kidney organoid on Day 16 of differentiation. The staining depicts the segmentation of nephron-like structures in the organoid at an early developmental stage. (Image courtesy of Tracy Tran\/McMahon Lab)<\/figcaption><\/figure>
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\u201cWhen I moved to USC from Harvard in 2012, I decided to focus all our efforts towards the kidney and human kidney disease. The support of the California Institute for Regenerative Medicine, as well as the National Institutes of Health, was essential to our change in direction. Realizing the need to bridge a critical gap between model systems and man, the group has pioneered systematic, high resolution molecular and cellular approaches to understand how this key organ is built. The research provides important information to guide efforts to understand this organ in health and disease, as well as to engineer human kidney structures in the laboratory. I have a wonderful team, and these four papers are a testament to their outstanding collaborative efforts,\u201d said McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.
\nCo-authors on the\u00a0JASN<\/em>\u00a0studies include: Jill A. McMahon, Jinjin Guo, Tracy Tran, Qiuyu Guo, Elisabeth Rutledge, Riana K. Parvez, Gohar Saribekyan, Robert E. Schuler, Christopher Liao, Albert D. Kim, Ahmed Abdelhalim, Seth W. Ruffins, Matthew E. Thornton, Brendan Grubbs, Guilherme De Sena Brandine, Andrew Ransick, Andrew D. Smith, and Carl Kesselman from USC; and Laurence Basking from the University of California, San Francisco.
\nFor the\u00a0JASN<\/em>\u00a0studies, support came from the California Institute for Regenerative Medicine (CIRM LA1-06536), the National Institutes of Health (NIH DK107350, DK094526, DK110792, 1U24DK110814), and the Joint Medical\/Research Council\/Wellcome Trust (099175\/Z\/12\/Z). Elisabeth Rutledge had a National Institute of Diabetes and Digestive and Kidney Disease Award (F31DK107216), Albert D. Kim had NIH support (5F32DK109616-02) and a USC Stem Cell Hearst Fellowship, and Qiuyu Guo had a USC Research Enhancement Fellowship.
\nCo-authors on the\u00a0PLoS Genetics<\/em>\u00a0study are: Qiuyu Guo, Emad Bahrami-Samani, Sean M. Hasso, Young-Jin Lee, Alan Fang, Albert D. Kim, Jinjin Guo, Andrew D. Smith, and Anton Valouev from USC; Joo-Seop Park from Cincinnati Children\u2019s Hospital Medical Center; Trudy M. Hong, Scott Lozanoff and Ben Fogelgren from the University of Hawaii at Manoa; Kevin A. Peterson from the Jackson Laboratory in Bar Harbor, Maine; and Ramya Raviram and Bing Ren from the University of California, San Diego.
\nFor the\u00a0PLoS Genetics<\/em>\u00a0research, funding was from the National Institutes of Health (DK054364, DK094526, DK085959, DK100315, HG006015, DK087852, DK100738, GM103457-8293) and the March of Dimes (5-FY14-56). O\u2019Brien had a USC Stem Cell Broad Postdoctoral Fellowship, and Qiuyu Gong had a CIRM fellowship.<\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"

Researchers are hard at work building mini-kidneys from human cells \u2014 using blueprints mostly drawn from lab mice. But mouse kidneys differ from their human counterparts in more than mere scale, as detailed by the USC Stem Cell laboratory of Andy McMahon in three studies in the Journal of the American Society of Nephrology.<\/p>\n","protected":false},"author":168,"featured_media":2156,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[436],"class_list":["post-2154","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-usc-stem-cell"],"acf":[],"yoast_head":"\nNever accept a kidney donation from a mouse<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/keck.usc.edu\/news\/never-accept-a-kidney-donation-from-a-mouse\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Never accept a kidney donation from a mouse\" \/>\n<meta property=\"og:description\" content=\"Researchers are hard at work building mini-kidneys from human cells \u2014 using blueprints mostly drawn from lab mice. 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