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A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations
Basement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins and their animal orthologs localized to...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116610/ https://www.ncbi.nlm.nih.gov/pubmed/35584218 http://dx.doi.org/10.1126/sciadv.abn2265 |
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author | Jayadev, Ranjay Morais, Mychel R. P. T. Ellingford, Jamie M. Srinivasan, Sandhya Naylor, Richard W. Lawless, Craig Li, Anna S. Ingham, Jack F. Hastie, Eric Chi, Qiuyi Fresquet, Maryline Koudis, Nikki-Maria Thomas, Huw B. O’Keefe, Raymond T. Williams, Emily Adamson, Antony Stuart, Helen M. Banka, Siddharth Smedley, Damian Sherwood, David R. Lennon, Rachel |
author_facet | Jayadev, Ranjay Morais, Mychel R. P. T. Ellingford, Jamie M. Srinivasan, Sandhya Naylor, Richard W. Lawless, Craig Li, Anna S. Ingham, Jack F. Hastie, Eric Chi, Qiuyi Fresquet, Maryline Koudis, Nikki-Maria Thomas, Huw B. O’Keefe, Raymond T. Williams, Emily Adamson, Antony Stuart, Helen M. Banka, Siddharth Smedley, Damian Sherwood, David R. Lennon, Rachel |
author_sort | Jayadev, Ranjay |
collection | PubMed |
description | Basement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins and their animal orthologs localized to BMs. Network analysis and screening in C. elegans and zebrafish uncovered BM regulators, including ADAMTS, ROBO, and TGFβ. More than 100 BM network genes associate with human phenotypes, and by screening 63,039 genomes from families with rare disorders, we found loss-of-function variants in LAMA5, MPZL2, and MATN2 and show that they regulate BM composition and function. This cross-disciplinary study establishes the immense complexity of BMs and their impact on in human health. |
format | Online Article Text |
id | pubmed-9116610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-91166102022-06-01 A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations Jayadev, Ranjay Morais, Mychel R. P. T. Ellingford, Jamie M. Srinivasan, Sandhya Naylor, Richard W. Lawless, Craig Li, Anna S. Ingham, Jack F. Hastie, Eric Chi, Qiuyi Fresquet, Maryline Koudis, Nikki-Maria Thomas, Huw B. O’Keefe, Raymond T. Williams, Emily Adamson, Antony Stuart, Helen M. Banka, Siddharth Smedley, Damian Sherwood, David R. Lennon, Rachel Sci Adv Biomedicine and Life Sciences Basement membranes (BMs) are ubiquitous extracellular matrices whose composition remains elusive, limiting our understanding of BM regulation and function. By developing a bioinformatic and in vivo discovery pipeline, we define a network of 222 human proteins and their animal orthologs localized to BMs. Network analysis and screening in C. elegans and zebrafish uncovered BM regulators, including ADAMTS, ROBO, and TGFβ. More than 100 BM network genes associate with human phenotypes, and by screening 63,039 genomes from families with rare disorders, we found loss-of-function variants in LAMA5, MPZL2, and MATN2 and show that they regulate BM composition and function. This cross-disciplinary study establishes the immense complexity of BMs and their impact on in human health. American Association for the Advancement of Science 2022-05-18 /pmc/articles/PMC9116610/ /pubmed/35584218 http://dx.doi.org/10.1126/sciadv.abn2265 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Jayadev, Ranjay Morais, Mychel R. P. T. Ellingford, Jamie M. Srinivasan, Sandhya Naylor, Richard W. Lawless, Craig Li, Anna S. Ingham, Jack F. Hastie, Eric Chi, Qiuyi Fresquet, Maryline Koudis, Nikki-Maria Thomas, Huw B. O’Keefe, Raymond T. Williams, Emily Adamson, Antony Stuart, Helen M. Banka, Siddharth Smedley, Damian Sherwood, David R. Lennon, Rachel A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title | A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title_full | A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title_fullStr | A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title_full_unstemmed | A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title_short | A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
title_sort | basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116610/ https://www.ncbi.nlm.nih.gov/pubmed/35584218 http://dx.doi.org/10.1126/sciadv.abn2265 |
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