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Your search keyword '"McMahon, Andrew P."' showing total 817 results
Start Over Author "McMahon, Andrew P." Publication Type Academic Journals
817 results on '"McMahon, Andrew P."'

3. Direct androgen receptor control of sexually dimorphic gene expression in the mammalian kidney

Author

Xiong, Lingyun, Liu, Jing, Han, Seung Yub, Koppitch, Kari, Guo, Jin-Jin, Rommelfanger, Megan, Miao, Zhen, Gao, Fan, Hallgrimsdottir, Ingileif B, Pachter, Lior, Kim, Junhyong, MacLean, Adam L, and McMahon, Andrew P

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Kidney Disease, Biotechnology, Prevention, Estrogen, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, 1.1 Normal biological development and functioning, Renal and urogenital, androgen receptor regulation, kidney, multiomic, proximal tubule, sexual dimorphism, single nuclear, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Mammalian organs exhibit distinct physiology, disease susceptibility, and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA sequencing (RNA-seq) data demonstrated that sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR)-mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation, whereas analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, disease, and metabolic linkage of sexually dimorphic gene activity.

Published
2023

6. A genetic model for in vivo proximity labelling of the mammalian secretome

Author

Yang, Rui, Meyer, Amanda S, Droujinine, Ilia A, Udeshi, Namrata D, Hu, Yanhui, Guo, Jinjin, McMahon, Jill A, Carey, Dominique K, Xu, Charles, Fang, Qiao, Sha, Jihui, Qin, Shishang, Rocco, David, Wohlschlegel, James, Ting, Alice Y, Carr, Steven A, Perrimon, Norbert, and McMahon, Andrew P

Subjects
Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Biotinylation, Mammals, Mass Spectrometry, Mice, Models, Genetic, Proteomics, Secretome, proximity-labelling, BirA, TurboID, secretome, inter-organ communication, serum proteins, Microbiology, Immunology, Biological sciences, Biomedical and clinical sciences
Abstract

Organ functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalysed proximity labelling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labelling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte-specific activation of BirA*G3 highlighted liver-specific biotinylated secretome profiles. The BirA*G3 mouse model demonstrates enhanced labelling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and in healthy and diseased adult states.

Published
2022

7. Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease

Author

Huang, Biao, Zeng, Zipeng, Kim, Sunghyun, Fausto, Connor C., Koppitch, Kari, Li, Hui, Li, Zexu, Chen, Xi, Guo, Jinjin, Zhang, Chennan C., Ma, Tianyi, Medina, Pedro, Schreiber, Megan E., Xia, Mateo W., Vonk, Ariel C., Xiang, Tianyuan, Patel, Tadrushi, Li, Yidan, Parvez, Riana K., Der, Balint, Chen, Jyun Hao, Liu, Zhenqing, Thornton, Matthew E., Grubbs, Brendan H., Diao, Yarui, Dou, Yali, Gnedeva, Ksenia, Ying, Qilong, Pastor-Soler, Nuria M., Fei, Teng, Hallows, Kenneth R., Lindström, Nils O., McMahon, Andrew P., and Li, Zhongwei

Published
2024
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9. Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter

Author

Kim, Albert D, Lake, Blue B, Chen, Song, Wu, Yan, Guo, Jinjin, Parvez, Riana K, Tran, Tracy, Thornton, Matthew E, Grubbs, Brendan, McMahon, Jill A, Zhang, Kun, and McMahon, Andrew P

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Kidney Disease, Underpinning research, 1.1 Normal biological development and functioning, Renal and urogenital, Cell Biology, Developmental Biology, Omics
Abstract

Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney's filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types.

Published
2019

19. Spatial transcriptional mapping of the human nephrogenic program

Author

Lindström, Nils O., Sealfon, Rachel, Chen, Xi, Parvez, Riana K., Ransick, Andrew, De Sena Brandine, Guilherme, Guo, Jinjin, Hill, Bill, Tran, Tracy, Kim, Albert D., Zhou, Jian, Tadych, Alicja, Watters, Aaron, Wong, Aaron, Lovero, Elizabeth, Grubbs, Brendan H., Thornton, Matthew E., McMahon, Jill A., Smith, Andrew D., Ruffins, Seth W., Armit, Chris, Troyanskaya, Olga G., and McMahon, Andrew P.

Published
2021
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20. A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking

Author

Minegishi, Katsura, Hashimoto, Masakazu, Ajima, Rieko, Takaoka, Katsuyoshi, Shinohara, Kyosuke, Ikawa, Yayoi, Nishimura, Hiromi, McMahon, Andrew P, Willert, Karl, Okada, Yasushi, Sasaki, Hiroshi, Shi, Dongbo, Fujimori, Toshihiko, Ohtsuka, Toshihisa, Igarashi, Yasunobu, Yamaguchi, Terry P, Shimono, Akihiko, Shiratori, Hidetaka, and Hamada, Hiroshi

Subjects
Biochemistry and Cell Biology, Biological Sciences, Adaptor Proteins, Signal Transducing, Animals, Body Patterning, Cell Communication, Cell Polarity, Intracellular Signaling Peptides and Proteins, LIM Domain Proteins, Membrane Proteins, Mice, Mice, Mutant Strains, Models, Biological, Proteins, Signal Transduction, Wnt Proteins, Wnt-5a Protein, Sfrp, Wnt, basal body, breaking of left-right symmetry, cilia, planar cell polarity, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a-/-Wnt5b-/- and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process. The absence of planar cell polarity (PCP) core proteins Prickle1 and Prickle2 in individual cells or local forced expression of Wnt5a perturbed polarization of neighboring wild-type cells. Our results suggest that opposing gradients of Wnt5a and Wnt5b and of their Sfrp inhibitors, together with intercellular signaling via PCP proteins, polarize node cells along the anterior-posterior axis for breaking of left-right symmetry.

Published
2017

21. Cadherin adhesion complexes direct cell aggregation in the epithelial transition of Wnt-induced nephron progenitor cells.

Author

Der, Balint, Bugacov, Helena, Briantseva, Bohdana-Myroslava, and McMahon, Andrew P.

Subjects
EPITHELIAL-mesenchymal transition, CELL aggregation, KIDNEY tubules, PROGENITOR cells, CADHERINS
Abstract

In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a ß-catenin (Ctnnb1)-driven, transcriptional nephrogenic program and the mesenchymal to epithelial transition (MET) of NPCs. Using an in vitro mouse NPC culturemodel, we observed that activation of the Wnt pathway results in the aggregation of induced NPCs, which is an initiating step in the MET program. Genetic removal showed aggregation was dependent on ß-catenin. Modulating extracellular Ca2+ levels showed cell-cell contacts were Ca2+ dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identified Cdh2, Cdh4 and Cdh11 in NPCs, and the ß-catenin directed upregulation of Cdh3 and Cdh4 accompanying the MET of induced NPCs. Mutational analysis of ß-catenin supported a role for a Lef/Tcf-ß-cateninmediated transcriptional response in the cell aggregation process. Genetic removal of all four cadherins, and independent removal of a-catenin or of ß-catenin-a-catenin interactions, abolished aggregation, but not the inductive response to Wnt pathway activation. These findings, and data in an accompanying article highlight the role of ß-catenin in linking transcriptional programs to the morphogenesis of NPCs in mammalian nephrogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Dose-dependent responses to canonical Wnt transcriptional complexes in the regulation of mammalian nephron progenitors.

Author

Bugacov, Helena, Der, Balint, Briantseva, Bohdana-Myroslava, Qiuyu Guo, Sunghyun Kim, Lindström, Nils O., and McMahon, Andrew P.

Subjects
GENE expression, PROGENITOR cells, KIDNEY tubules, GENETIC transcription regulation, CELL proliferation, WNT signal transduction
Abstract

In vivo and in vitro studies argue that concentration-dependent Wnt signaling regulates mammalian nephron progenitor cell (NPC) programs. Canonical Wnt signaling is regulated through the stabilization of ß-catenin, a transcriptional co-activator when complexed with Lef/Tcf DNA-binding partners. Using the GSK3ß inhibitor CHIR99021 (CHIR) to block GSK3ß-dependent destruction of ß-catenin, we examined dose-dependent responses to ß-catenin in mouse NPCs, using mRNA transduction to modify gene expression. Low CHIR-dependent proliferation of NPCs was blocked on ß-catenin removal, with evidence of NPCs arresting at the G2-M transition. While NPC identity was maintained following ß-catenin removal, mRNA-seq identified low CHIR and ß-catenin dependent genes. High CHIR activated nephrogenesis. Nephrogenic programming was dependent on Lef/Tcf factors and ß-catenin transcriptional activity. Molecular and cellular features of early nephrogenesis were driven in the absence of CHIR by a mutated stabilized form of ß-catenin. Chromatin association studies indicate low and high CHIR response genes are likely direct targets of canonical Wnt transcriptional complexes. Together, these studies provide evidence for concentration-dependent Wnt signaling in the regulation of NPCs and provide new insight into Wnt targets initiating mammalian nephrogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality

Author

Legouis, David, Ricksten, Sven-Erick, Faivre, Anna, Verissimo, Thomas, Gariani, Karim, Verney, Charles, Galichon, Pierre, Berchtold, Lena, Feraille, Eric, Fernandez, Marylise, Placier, Sandrine, Koppitch, Kari, Hertig, Alexandre, Martin, Pierre-Yves, Naesens, Maarten, Pugin, Jérôme, McMahon, Andrew P., Cippà, Pietro E., and de Seigneux, Sophie

Published
2020
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25. Proteomics of protein trafficking by in vivo tissue-specific labeling

Author

Droujinine, Ilia A., Meyer, Amanda S., Wang, Dan, Udeshi, Namrata D., Hu, Yanhui, Rocco, David, McMahon, Jill A., Yang, Rui, Guo, JinJin, Mu, Luye, Carey, Dominique K., Svinkina, Tanya, Zeng, Rebecca, Branon, Tess, Tabatabai, Areya, Bosch, Justin A., Asara, John M., Ting, Alice Y., Carr, Steven A., McMahon, Andrew P., and Perrimon, Norbert

Published
2021
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33. Retinoid Signaling in Progenitors Controls Specification and Regeneration of the Urothelium

Author

Gandhi, Devangini, Molotkov, Andrei, Batourina, Ekatherina, Schneider, Kerry, Dan, Hanbin, Reiley, Maia, Laufer, Ed, Metzger, Daniel, Liang, Fengxia, Liao, Yi, Sun, Tung-Tien, Aronow, Bruce, Rosen, Roni, Mauney, Josh, Adam, Rosalyn, Rosselot, Carolina, Van Batavia, Jason, McMahon, Andrew, McMahon, Jill, Guo, Jin-Jin, and Mendelsohn, Cathy

Subjects
Stem Cell Research, Urologic Diseases, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Animals, Biological Transport, Cell Differentiation, Epithelium, Gene Expression Regulation, Developmental, Humans, Keratin-5, Mice, Regeneration, Stem Cells, Urinary Tract, Uroplakins, Urothelium, Wound Healing, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome.

Published
2013

46. Mouse Brain Organization Revealed through Direct Genome-Scale TF Expression Analysis

Author

Gray, Paul A., Fu, Hui, Luo, Ping, Zhao, Qing, Yu, Jing, Ferrari, Annette, Tenzen, Toyoaki, Yuk, Dong-in, Tsung, Eric F., Cai, Zhaohui, Alberta, John A., Cheng, Le-ping, Liu, Yang, Stenman, Jan M., Valerius, M. Todd, Billings, Nathan, Kim, Haesun A., Greenberg, Michael E., McMahon, Andrew P., Rowitch, David H., Stiles, Charles D., and Ma, Qiufu

Published
2004

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