Faculty Bibliography
Searched for:
Department/Unit:Cell Biology
Total Results:
14241
Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency
Gpr125 is an orphan G-protein coupled receptor, with homology to cell adhesion and axonal guidance factors, that is implicated in planar polarity and control of cell movements. By lineage tracing we demonstrate that Gpr125 is a highly specific marker of bipotent mammary stem cells in the embryo and of multiple long-lived unipotent basal mammary progenitors in perinatal and postnatal glands. Nipple-proximal Gpr125+ cells express a transcriptomic profile indicative of chemo-repulsion and cell movement, whereas Gpr125+ cells concentrated at invasive ductal tips display a hybrid epithelial-mesenchymal phenotype and are equipped to bind chemokine and growth factors and secrete a promigratory matrix. Gpr125 progenitors acquire bipotency in the context of transplantation and cancer and are greatly expanded and massed at the pushing margins of short latency MMTV-Wnt1 tumors. High Gpr125 expression identifies patients with particularly poor outcome within the basal breast cancer subtype highlighting its potential utility as a factor to stratify risk.
PMID: 35302059
ISSN: 2041-1723
CID: 5181672
Radon-222 Brain Dosimetry
ABSTRACT/UNASSIGNED:The human brain dose from radon-222 (222Rn) exposure is calculated here using 222Rn tissue solubility data. A fraction of 222Rn inhaled dissolves in blood and cellular fluids and circulates to brain and all organs. Radon-222 has a relatively high solubility in blood and body fluids based on human inhalation experiments. The brain dose uses calculated concentrations of 222Rn in blood and cellular fluids from exhaled breath measurements following human exposure in a 222Rn chamber. The annual brain dose from continuous inhalation of a concentration of 100 Bq m-3 is about 450 times less than the dose to bronchial epithelium from inhalation of the same 222Rn concentration. Based on the 222Rn dosimetry here, it is highly unlikely that brain cancer is related to even high 222Rn exposures. Any functional or neurodegenerative issues from exposure to very small doses of 222Rn alpha particles are, at present, unknown.
PMID: 35228505
ISSN: 1538-5159
CID: 5174242
Luminal Oxidative Regulation of the Ryanodine Receptor: More Sides to the Story? [Editorial]
PMID: 35239403
ISSN: 1524-4571
CID: 5174622
LPGAT1 controls the stearate/palmitate ratio of phosphatidylethanolamine and phosphatidylcholine in sn-1 specific remodeling
Most mammalian phospholipids contain a saturated fatty acid at the sn-1 carbon atom and an unsaturated fatty acid at the sn-2 carbon atom of the glycerol backbone group. While the sn-2 linked chains undergo extensive remodeling by deacylation and reacylation (Lands cycle), it is not known how the composition of saturated fatty acids is controlled at the sn-1 position. Here, we demonstrate that lysophosphatidylglycerol acyltransferase 1 (LPGAT1) is an sn-1 specific acyltransferase that controls the stearate/palmitate ratio of phosphatidylethanolamine (PE) and phosphatidylcholine. Bacterially expressed murine LPGAT1 transferred saturated acyl-CoAs specifically into the sn-1 position of lysophosphatidylethanolamine (LPE) rather than lysophosphatidylglycerol and preferred stearoyl-CoA over palmitoyl-CoA as the substrate. In addition, genetic ablation of LPGAT1 in mice abolished 1-LPE:stearoyl-CoA acyltransferase activity and caused a shift from stearate to palmitate species in PE, dimethyl-PE, and phosphatidylcholine. Lysophosphatidylglycerol acyltransferase 1 KO mice were leaner and had a shorter life span than their littermate controls. Finally, we show that total lipid synthesis was reduced in isolated hepatocytes of LPGAT1 knockout mice. Thus, we conclude that LPGAT1 is an sn-1 specific LPE acyltransferase that controls the stearate/palmitate homeostasis of PE and the metabolites of the PE methylation pathway and that LPGAT1 plays a central role in the regulation of lipid biosynthesis with implications for body fat content and longevity.
PMID: 35131264
ISSN: 1083-351x
CID: 5175992
Multiple eruptive dermatofibromas in an adolescent with a history of pityriasis lichenoides et varioliformis acuta [Case Report]
PMCID:8816644
PMID: 35141383
ISSN: 2352-5126
CID: 5176102
Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm
Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there is no proven drug treatment for this condition. In this study, by using the Connectivity Map (CMap) approach, we explored naringenin, a naturally occurring citrus flavonoid, as a putative agent for inhibiting AAA. We then validated the prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice and angiotensin II-infused ApoE-/- mice. Naringenin effectively blocked the formation of AAAs and the progression of established AAAs. Transcription factor EB (TFEB) is the master regulator of lysosome biogenesis. Intriguingly, the protective role of naringenin on AAA was abolished by macrophage-specific TFEB depletion in mice. Unbiased interactomics, combined with isothermal titration calorimetry (ITC) and cellular thermal shift assays (CETSAs), further revealed that naringenin is directly bound to 14-3-3 epsilon blocked the TFEB-14-3-3 epsilon interaction, and therefore promoted TFEB nuclear translocation and activation. On one hand, naringenin activated lysosome-dependent inhibition of the NLRP3 inflammasome and repressed aneurysmal inflammation. On the other hand, naringenin induced TFEB-dependent transcriptional activation of GATA3, IRF4, and STAT6 and therefore promoted reparative M2 macrophage polarization. In summary, naturally derived naringenin or macrophage TFEB activation shows promising efficacy for the treatment of AAA.
PMID: 35228523
ISSN: 2056-5968
CID: 5174252
Artificial intelligence and deep learning to map immune cell types in inflamed human tissue
Biopsies of inflammatory tissue contain a complex network of interacting cells, orchestrating the immune or autoimmune response. While standard histological examination can identify relationships, it is clear that a great amount of data on each slide is not quantitated or categorized in standard microscopic examinations. To deal with the huge amount of data present in biopsy tissue in an unbiased and comprehensive way, we have developed a deep learning algorithm to identify immune cells in biopsies of inflammatory lesions. We focused on T follicular helper (Tfh) cell subsets and B cells in dermatomyositis biopsy images. We achieved strong performance on detection and classification of cells, including the rare Tfh cell subsets present in the tissue. This algorithm could be used to perform distance mapping between cell types in tissue, and could be easily adapted to other disease states.
PMID: 35131237
ISSN: 1872-7905
CID: 5175982
Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly
For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.
PMID: 35239393
ISSN: 1095-9203
CID: 5174612
Gender disparities in editorial board of academic urology journals [Meeting Abstract]
Introduction & Objectives: Gender composition within surgical academic leadership, including academic medical journals, disproportionately favors men. Disparities in journal leadership may introduce bias due to the familiar nature of reviewing and accepting academic publications. Genderrepresentation among academic urological journals' editorial boards has not yet been assessed. We evaluated female representation on editorialboards of urologic journals across multiple countries.Materials & Methods: Urologic journal leadership appointees' names and position descriptions were collected (from what pool? Did you surveyevery academic urology journal in the world?). Probable gender was obtained using gender-api.com or through personal title, as available. Journaleditorial positions were aggregated into broad leadership categories. Journal characteristics were summarized by Scimago Journal quartile (3 year,algorithmic weighted citation ranking) and geographic area. Chi-square test and multivariate logistic regression analysis were performed to assessfemale gender representation (p<0.05 significant).
Result(s): A total of 105 journals were reviewed with 5,991 total members: 877 (14.6%) female, 5,112 (85.3%) male and 2 (0.03%) non-binarypersons. Female representation significantly differed by leadership position, journal ranking, and geographic region. Editors-in-chief roles had thelowest female representation (48 females, 12.1%), while non-academic (32 females, 40.5%) and administrative (4 females, 80%) positions werehighest. Female representation, by journal ranking, was highest in Q1 (417 females, 19.4%) and lowest in Q3 (133 females, 8.9%) and by region,was highest in North American (323 females, 23.0%) and lowest in Asiatic region journals (55 females, 6.6%). On multivariate logistic regressionanalysis, Q1 journals had higher odds of female representation compared to Q2 and Q3. Additionally, compared to Western Europe, North Americanjournals had 78% higher odds and Asiatic journals had 50% lower odds of female representation (Fig 1).(Figure Presented)Conclusions: Female representation in urologic journal leadership is low across all journals, although trends in their proportion were identified by journal quartile and region. Addressing this gender imbalance may improve equal gender representation in journals and likely also improve female authored publication rates
Copyright
Result(s): A total of 105 journals were reviewed with 5,991 total members: 877 (14.6%) female, 5,112 (85.3%) male and 2 (0.03%) non-binarypersons. Female representation significantly differed by leadership position, journal ranking, and geographic region. Editors-in-chief roles had thelowest female representation (48 females, 12.1%), while non-academic (32 females, 40.5%) and administrative (4 females, 80%) positions werehighest. Female representation, by journal ranking, was highest in Q1 (417 females, 19.4%) and lowest in Q3 (133 females, 8.9%) and by region,was highest in North American (323 females, 23.0%) and lowest in Asiatic region journals (55 females, 6.6%). On multivariate logistic regressionanalysis, Q1 journals had higher odds of female representation compared to Q2 and Q3. Additionally, compared to Western Europe, North Americanjournals had 78% higher odds and Asiatic journals had 50% lower odds of female representation (Fig 1).(Figure Presented)Conclusions: Female representation in urologic journal leadership is low across all journals, although trends in their proportion were identified by journal quartile and region. Addressing this gender imbalance may improve equal gender representation in journals and likely also improve female authored publication rates
Copyright
EMBASE:2016657896
ISSN: 1873-7560
CID: 5173232
Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility
Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.
PMID: 35210625
ISSN: 1546-1718
CID: 5172442
