دورية أكاديمية
Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease.
| العنوان: | Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease. |
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| المؤلفون: | Yousef Yengej FA; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Pou Casellas C; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Ammerlaan CME; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Olde Hanhof CJA; Department of Medical BioSciences, Radboud Institute for Medical Innovation, 6525 GA Nijmegen, the Netherlands., Dilmen E; Department of Medical BioSciences, Radboud Institute for Medical Innovation, 6525 GA Nijmegen, the Netherlands., Beumer J; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW, 3584 CT Utrecht, the Netherlands; Institute of Human Biology, Roche Pharma Research and Early Development, 4058 Basel, Switzerland., Begthel H; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW, 3584 CT Utrecht, the Netherlands., Meeder EMG; Department of Psychiatry, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands., Hoenderop JG; Department of Medical BioSciences, Radboud Institute for Medical Innovation, 6525 GA Nijmegen, the Netherlands., Rookmaaker MB; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Verhaar MC; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands. Electronic address: m.c.verhaar@umcutrecht.nl., Clevers H; Hubrecht Institute for Developmental Biology and Stem Cell Research-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute-KNAW, 3584 CT Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu. |
| المصدر: | Cell reports [Cell Rep] 2024 Jan 23; Vol. 43 (1), pp. 113614. Date of Electronic Publication: 2023 Dec 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Lithium*/pharmacology , Aquaporin 2*, Adult ; Humans ; Nephrons ; Kidney ; Electrolytes ; Organoids |
| مستخلص: | Organoid technology is rapidly gaining ground for studies on organ (patho)physiology. Tubuloids are long-term expanding organoids grown from adult kidney tissue or urine. The progenitor state of expanding tubuloids comes at the expense of differentiation. Here, we differentiate tubuloids to model the distal nephron and collecting ducts, essential functional parts of the kidney. Differentiation suppresses progenitor traits and upregulates genes required for function. A single-cell atlas reveals that differentiation predominantly generates thick ascending limb and principal cells. Differentiated human tubuloids express luminal NKCC2 and ENaC capable of diuretic-inhibitable electrolyte uptake and enable disease modeling as demonstrated by a lithium-induced tubulopathy model. Lithium causes hallmark AQP2 loss, induces proliferation, and upregulates inflammatory mediators, as seen in vivo. Lithium also suppresses electrolyte transport in multiple segments. In conclusion, this tubuloid model enables modeling of the human distal nephron and collecting duct in health and disease and provides opportunities to develop improved therapies. Competing Interests: Declaration of interests H.C. is inventor on several patents related to organoid technology; his full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. has been head of Pharma Research and Early Development of Roche in Basel, Switzerland, since March 2022. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: CP: Stem cell research; RNA sequencing; kidney organoid; lithium; loop of Henle; nephron; principal cells; stem cells; tubuloid |
| المشرفين على المادة: | 9FN79X2M3F (Lithium) 0 (Aquaporin 2) 0 (Electrolytes) |
| تواريخ الأحداث: | Date Created: 20231230 Date Completed: 20240126 Latest Revision: 20240212 |
| رمز التحديث: | 20240213 |
| DOI: | 10.1016/j.celrep.2023.113614 |
| PMID: | 38159278 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2023.113614 |