LIVIVO - Search results -

Search results

Result 1 - 10 of total 10

Search options

Article ; Online: High-throughput translational profiling with riboPLATE-seq.

Metz, Jordan B / Hornstein, Nicholas J / Sharma, Sohani Das / Worley, Jeremy / Gonzalez, Christian / Sims, Peter A

2022 Volume 12, Issue 1, Page(s) 5718

Abstract: Protein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, ...

Abstract	Protein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, a scalable method for generating paired libraries of ribosome-associated and total mRNA. As an extension of the PLATE-seq protocol, riboPLATE-seq utilizes barcoded primers for pooled library preparation, but additionally leverages anti-rRNA ribosome immunoprecipitation on whole polysomes to measure ribosome association (RA). We compare RA to its analogue in ribosome profiling and RNA sequencing, translation efficiency, and demonstrate both the performance of riboPLATE-seq and its utility in detecting translational alterations induced by specific inhibitors of protein kinases.
MeSH term(s)	High-Throughput Nucleotide Sequencing/methods ; Polyribosomes/genetics ; Polyribosomes/metabolism ; Protein Biosynthesis ; Ribosomes/genetics ; Ribosomes/metabolism ; Sequence Analysis, RNA/methods
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09638-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

Cancer cell

2023 Volume 41, Issue 11, Page(s) 1972–1988.e5

Abstract: When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in ... ...

Abstract	When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients.
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Androgen Antagonists/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Androgens/therapeutic use ; Immunotherapy ; Castration ; Tumor Microenvironment
Chemical Substances	Androgen Antagonists ; Androgens
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2023.10.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

Order via subito

Details ▾

Article ; Online: Inositol pyrophosphates regulate cell growth and the environmental stress response by activating the HDAC Rpd3L.

Worley, Jeremy / Luo, Xiangxia / Capaldi, Andrew P

Cell reports

2013 Volume 3, Issue 5, Page(s) 1476–1482

Abstract: Cells respond to stress and starvation by adjusting their growth rate and enacting stress defense programs. In eukaryotes this involves inactivation of TORC1, which in turn triggers downregulation of ribosome and protein synthesis genes and upregulation ... ...

Abstract	Cells respond to stress and starvation by adjusting their growth rate and enacting stress defense programs. In eukaryotes this involves inactivation of TORC1, which in turn triggers downregulation of ribosome and protein synthesis genes and upregulation of stress response genes. Here we report that the highly conserved inositol pyrophosphate (PP-IP) second messengers (including 1-PP-IP5, 5-PP-IP4, and 5-PP-IP5) are also critical regulators of cell growth and the general stress response, acting in parallel with the TORC1 pathway to control the activity of the class I histone deacetylase Rpd3L. In fact, yeast cells that cannot synthesize any of the PP-IPs mount little to no transcriptional response to osmotic, heat, or oxidative stress. Furthermore, PP-IP-dependent regulation of Rpd3L occurs independently of the role individual PP-IPs (such as 5-PP-IP5) play in activating specialized stress/starvation response pathways. Thus, the PP-IP second messengers simultaneously activate and tune the global response to stress and starvation signals.
MeSH term(s)	Gene Expression Regulation, Fungal/drug effects ; Histone Deacetylase 1/genetics ; Histone Deacetylase 1/metabolism ; Inositol Phosphates/pharmacology ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes/metabolism ; Osmolar Concentration ; Oxidative Stress ; Phosphotransferases (Phosphate Group Acceptor)/genetics ; Phosphotransferases (Phosphate Group Acceptor)/metabolism ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/growth & development ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Second Messenger Systems ; TOR Serine-Threonine Kinases/metabolism ; Temperature
Chemical Substances	Inositol Phosphates ; Multiprotein Complexes ; Saccharomyces cerevisiae Proteins ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Phosphotransferases (Phosphate Group Acceptor) (EC 2.7.4.-) ; KCS1 protein, S cerevisiae (EC 2.7.4.21) ; inositol hexakisphosphate kinase (EC 2.7.4.21) ; Histone Deacetylase 1 (EC 3.5.1.98)
Language	English
Publishing date	2013-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2013.03.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The Master Regulator Protein BAZ2B Can Reprogram Human Hematopoietic Lineage-Committed Progenitors into a Multipotent State.

Arumugam, Karthik / Shin, William / Schiavone, Valentina / Vlahos, Lukas / Tu, Xiaochuan / Carnevali, Davide / Kesner, Jordan / Paull, Evan O / Romo, Neus / Subramaniam, Prem / Worley, Jeremy / Tan, Xiangtian / Califano, Andrea / Cosma, Maria Pia

Cell reports

2020 Volume 33, Issue 10, Page(s) 108474

Abstract: Bi-species, fusion-mediated, somatic cell reprogramming allows precise, organism-specific tracking of unknown lineage drivers. The fusion of ... ...

Abstract	Bi-species, fusion-mediated, somatic cell reprogramming allows precise, organism-specific tracking of unknown lineage drivers. The fusion of Tcf7l1
MeSH term(s)	Animals ; B-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Cellular Reprogramming/genetics ; Cellular Reprogramming/physiology ; Cord Blood Stem Cell Transplantation/methods ; Female ; Fetal Blood/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/metabolism ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Multipotent Stem Cells/metabolism ; Transcription Factors/metabolism ; Transcription Factors, General/genetics ; Transcription Factors, General/metabolism ; Transcription Factors, General/physiology
Chemical Substances	BAZ2B protein, human ; Transcription Factors ; Transcription Factors, General
Language	English
Publishing date	2020-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.108474
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Genome-Wide Analysis of the TORC1 and Osmotic Stress Signaling Network in Saccharomyces cerevisiae.

Worley, Jeremy / Sullivan, Arron / Luo, Xiangxia / Kaplan, Matthew E / Capaldi, Andrew P

G3 (Bethesda, Md.)

2015 Volume 6, Issue 2, Page(s) 463–474

Abstract: The Target of Rapamycin kinase Complex I (TORC1) is a master regulator of cell growth and metabolism in eukaryotes. Studies in yeast and human cells have shown that nitrogen/amino acid starvation signals act through Npr2/Npr3 and the small GTPases Gtr1/ ... ...

Abstract	The Target of Rapamycin kinase Complex I (TORC1) is a master regulator of cell growth and metabolism in eukaryotes. Studies in yeast and human cells have shown that nitrogen/amino acid starvation signals act through Npr2/Npr3 and the small GTPases Gtr1/Gtr2 (Rags in humans) to inhibit TORC1. However, it is unclear how other stress and starvation stimuli inhibit TORC1, and/or act in parallel with the TORC1 pathway, to control cell growth. To help answer these questions, we developed a novel automated pipeline and used it to measure the expression of a TORC1-dependent ribosome biogenesis gene (NSR1) during osmotic stress in 4700 Saccharomyces cerevisiae strains from the yeast knock-out collection. This led to the identification of 440 strains with significant and reproducible defects in NSR1 repression. The cell growth control and stress response proteins deleted in these strains form a highly connected network, including 56 proteins involved in vesicle trafficking and vacuolar function; 53 proteins that act downstream of TORC1 according to a rapamycin assay--including components of the HDAC Rpd3L, Elongator, and the INO80, CAF-1 and SWI/SNF chromatin remodeling complexes; over 100 proteins involved in signaling and metabolism; and 17 proteins that directly interact with TORC1. These data provide an important resource for labs studying cell growth control and stress signaling, and demonstrate the utility of our new, and easily adaptable, method for mapping gene regulatory networks.
MeSH term(s)	Cluster Analysis ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Gene Knockout Techniques ; Gene Regulatory Networks ; Genome, Fungal ; Genome-Wide Association Study ; Genomics/methods ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Mutation ; Osmotic Pressure ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Signal Transduction ; Stress, Physiological/genetics ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Multiprotein Complexes ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2015-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1534/g3.115.025882
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Details ▾
- Full text online
- Order with fees

Article: OPHIDIOMYCES OPHIODIICOLA ON A CAPTIVE BLACK RACER (COLUBER CONSTRICTOR) AND A GARTER SNAKE (THAMNOPHIS SIRTALIS) IN PENNSYLVANIA.

Ohkura, Mana / Worley, Jeremy J / Hughes-Hallett, James E / Fisher, Jenny S / Love, Brenda C / Arnold, A Elizabeth / Orbach, Marc J

Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians

2016 Volume 47, Issue 1, Page(s) 341–346

Abstract: Two snakes were presented to the Pennsylvania State University Animal Diagnostic Laboratory with one suffering from external lesions where the scales were raised and discolored, and the other with oral lesions and swelling extending to the left eye, ... ...

Abstract	Two snakes were presented to the Pennsylvania State University Animal Diagnostic Laboratory with one suffering from external lesions where the scales were raised and discolored, and the other with oral lesions and swelling extending to the left eye, which was opaque. Histopathological analysis revealed multifocal granulomas containing fungal hyphae. Morphological and DNA sequence analyses revealed both suffered from infection by Ophidiomyces ophiodiicola, an emerging pathogen of snakes. This is the first report of this disease in Pennsylvania.
MeSH term(s)	Animals ; Ascomycota/isolation & purification ; Mycoses/genetics ; Mycoses/microbiology ; Mycoses/veterinary ; Phylogeny ; Snakes/microbiology
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2174930-9
ISSN	1937-2825 ; 1042-7260
ISSN (online)	1937-2825
ISSN	1042-7260
DOI	10.1638/2015-0123.1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human.

Circulation

2020 Volume 142, Issue 21, Page(s) 2060–2075

Abstract: Background: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the ... ...

Abstract	Background: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. Methods: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. Results: We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability. Conclusions: Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.
MeSH term(s)	Animals ; Atherosclerosis/genetics ; Atherosclerosis/pathology ; Atherosclerosis/therapy ; Cell Dedifferentiation/physiology ; Cell Differentiation/physiology ; Cell Movement/physiology ; Cell Transdifferentiation/physiology ; Cells, Cultured ; Female ; Genetic Therapy/trends ; Genomics/methods ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Myocytes, Smooth Muscle/pathology ; Myocytes, Smooth Muscle/physiology ; Phenotype ; Sequence Analysis, RNA/methods
Keywords	covid19
Language	English
Publishing date	2020-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.120.048378
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui IV Zs.60: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations.

Affo, Silvia / Nair, Ajay / Brundu, Francesco / Ravichandra, Aashreya / Bhattacharjee, Sonakshi / Matsuda, Michitaka / Chin, LiKang / Filliol, Aveline / Wen, Wen / Song, Xinhua / Decker, Aubrianna / Worley, Jeremy / Caviglia, Jorge Matias / Yu, Lexing / Yin, Deqi / Saito, Yoshinobu / Savage, Thomas / Wells, Rebecca G / Mack, Matthias /

Zender, Lars / Arpaia, Nicholas / Remotti, Helen E / Rabadan, Raul / Sims, Peter / Leblond, Anne-Laure / Weber, Achim / Riener, Marc-Oliver / Stockwell, Brent R / Gaublomme, Jellert / Llovet, Josep M / Kalluri, Raghu / Michalopoulos, George K / Seki, Ekihiro / Sia, Daniela / Chen, Xin / Califano, Andrea / Schwabe, Robert F

Cancer cell

2021 Volume 39, Issue 6, Page(s) 883

Language	English
Publishing date	2021-06-15
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.05.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

Order via subito

Details ▾

Article ; Online: Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations.

Cancer cell

2021 Volume 39, Issue 6, Page(s) 866–882.e11

Abstract: Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell ... ...

Abstract	Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.
MeSH term(s)	Aged ; Animals ; Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic/pathology ; Cancer-Associated Fibroblasts/metabolism ; Cancer-Associated Fibroblasts/pathology ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/pathology ; Collagen Type I/metabolism ; Female ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/pathology ; Hepatocyte Growth Factor/metabolism ; Humans ; Hyaluronan Synthases/genetics ; Hyaluronan Synthases/metabolism ; Hyaluronic Acid/metabolism ; Male ; Mice, Transgenic ; Middle Aged ; Proto-Oncogene Proteins c-met/metabolism ; Tumor Microenvironment
Chemical Substances	Collagen Type I ; HGF protein, human ; Hepatocyte Growth Factor (67256-21-7) ; Hyaluronic Acid (9004-61-9) ; HAS2 protein, human (EC 2.4.1.212) ; Hyaluronan Synthases (EC 2.4.1.212) ; MET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2021-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.03.012
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

Order via subito

Details ▾

Article: Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human

Circulation

Abstract: Background: Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to ... ...

Abstract	Background: Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to pathophysiology of atherosclerosis remains elusive. Methods: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and employed pharmacological studies targeting SMC-derived cells both in vivo and in vitro. Results: We found that SMC transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells, were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return towards SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome wide association study (GWAS) signals for coronary artery disease (CAD) in RA signaling target gene loci and correlation between CAD risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans retinoic acid (ATRA), an anti-cancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden and promoted fibrous cap stability. Conclusions: Integration of cell-specific fate mapping, single-cell genomics and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32962412
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Kategorien

Inter-library loan at ZB MED