Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes.
AuthorsKane BJ, Zinner MJ, Yarmush ML, Toner M
JournalAnal Chem
PubMed ID16808435
'Nearly half a billion dollars in resources are lost each time a drug candidate is withdrawn from the market by the Food and Drug Administration (FDA) for reasons of liver toxicity. The number of late-phase drug developmental failures due to liver toxicity could potentially be reduced through the use of ... More
Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype.
AuthorsIssa A, Le TX, Shoushtari AN, Shields JD, Swartz MA,
JournalCancer Res
PubMed ID19118020
'Most carcinomas spread to distant sites through lymphatic vessels. Several preclinical and clinical studies have shown a positive correlation between the incidence of lymph node metastasis and secretion of the lymphatic growth factor vascular endothelial growth factor-C (VEGF-C) by tumor cells, suggesting tumor lymphangiogenesis as an escape mechanism. However, recent ... More
Editing antigen presentation: antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors.
AuthorsHarvey BP, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ,
JournalJ Immunol
PubMed ID18768860
'B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In ... More
Quantitative 3D video microscopy of HIV transfer across T cell virological synapses.
AuthorsHübner W, McNerney GP, Chen P, Dale BM, Gordon RE, Chuang FY, Li XD, Asmuth DM, Huser T, Chen BK,
JournalScience
PubMed ID19325119
The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV ... More
Coculture methodologies for the study of Wnt signals.
AuthorsPlanutis K, Planutiene M, Holcombe RF,
JournalMethods Mol Biol
PubMed ID19099261
In vivo, responses to extracellular Wnt ligands are context dependent; the temporal characteristics and intensity of the signal are critical in determining the target cell response. In general, Wnt ligand-induced differentiation in mammalian cells requires several days of exposure. In order to better characterize Wnt-induced signaling in vitro, side-by-side and ... More
Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment.
AuthorsMitoma J, Bao X, Petryanik B, Schaerli P, Gauguet JM, Yu SY, Kawashima H, Saito H, Ohtsubo K, Marth JD, Khoo KH, von Andrian UH, Lowe JB, Fukuda M
JournalNat Immunol
PubMed ID17334369
Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained ... More
Small molecule inhibitors of Clostridium difficile toxin B-induced cellular damage.
Clostridium difficile causes life-threatening diarrhea through the actions of its homologous toxins TcdA and TcdB on human colonocytes. Therapeutic agents that block toxin-induced damage are urgently needed to prevent the harmful consequences of toxin action that are not addressed with current antibiotic-based treatments. Here, we developed an imaging-based phenotypic screen ... More
Cell-cell electrofusion: optimization of electric field amplitude and hypotonic treatment for mouse melanoma (B16-F1) and Chinese Hamster ovary (CHO) cells.
AuthorsUsaj M, Trontelj K, Miklavcic D, Kanduser M,
JournalJ Membr Biol
PubMed ID20628737
Efficient electroporation of cells in physical contact induces cell fusion, and this process is known as electrofusion. It has been shown that appropriate hypotonic treatment of cells before the application of electric pulses can cause a significant increase in electrofusion efficiency. First, the amplitudes of the electric field were determined ... More
Sorting of the neuroendocrine secretory protein Secretogranin II into the regulated secretory pathway: role of N- and C-terminal alpha-helical domains.
AuthorsCourel M, Vasquez MS, Hook VY, Mahata SK, Taupenot L,
JournalJ Biol Chem
PubMed ID18299326
Secretogranin II (SgII) belongs to the granin family of prohormones widely distributed in dense-core secretory granules (DCGs) of endocrine, neuroendocrine, and neuronal cells, including sympathoadrenal chromaffin cells. The mechanisms by which secretory proteins, and granins in particular, are sorted into the regulated secretory pathway are unsettled. We designed a strategy ... More
Functional scaffold-free 3-D cardiac microtissues: a novel model for the investigation of heart cells.
AuthorsDesroches BR, Zhang P, Choi BR, King ME, Maldonado AE, Li W, Rago A, Liu G, Nath N, Hartmann KM, Yang B, Koren G, Morgan JR, Mende U,
JournalAm J Physiol Heart Circ Physiol
PubMed ID22427522
To bridge the gap between two-dimensional cell culture and tissue, various three-dimensional (3-D) cell culture approaches have been developed for the investigation of cardiac myocytes (CMs) and cardiac fibroblasts (CFs). However, several limitations still exist. This study was designed to develop a cardiac 3-D culture model with a scaffold-free technology ... More
Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes.
AuthorsSkokos D, Shakhar G, Varma R, Waite JC, Cameron TO, Lindquist RL, Schwickert T, Nussenzweig MC, Dustin ML
JournalNat Immunol
PubMed ID17632517
T cells survey antigen-presenting dendritic cells (DCs) by migrating through DC networks, arresting and maintaining contact with DCs for several hours after encountering high-potency complexes of peptide and major histocompatibility complex (pMHC), leading to T cell activation. The effects of low-potency pMHC complexes on T cells in vivo, however, are ... More
Condensation of the plasma membrane at the site of T lymphocyte activation.
AuthorsGaus K, Chklovskaia E, Fazekas de St Groth B, Jessup W, Harder T
JournalJ Cell Biol
PubMed ID16203859
After activation, T lymphocytes restructure their cell surface to form membrane domains at T cell receptor (TCR)-signaling foci and immunological synapses (ISs). To address whether these rearrangements involve alteration in the structure of the plasma membrane bilayer, we used the fluorescent probe Laurdan to visualize its lipid order. We observed ... More
Two-step engulfment of apoptotic cells.
AuthorsToda S, Hanayama R, Nagata S,
JournalMol Cell Biol
PubMed ID22037761
Apoptotic cells expose phosphatidylserine on their surface as an "eat me" signal, and macrophages respond by engulfing them. Although several molecules that specifically bind phosphatidylserine have been identified, the molecular mechanism that triggers engulfment remains elusive. Here, using a mouse pro-B cell line, Ba/F3, that grows in suspension, we reconstituted ... More
Fluorescently labeled collagen binding proteins allow specific visualization of collagen in tissues and live cell culture.
AuthorsKrahn KN, Bouten CV, van Tuijl S, van Zandvoort MA, Merkx M
JournalAnal Biochem
PubMed ID16476406
Visualization of the formation and orientation of collagen fibers in tissue engineering experiments is crucial for understanding the factors that determine the mechanical properties of tissues. In this study, collagen-specific fluorescent probes were developed using a new approach that takes advantage of the inherent specificity of collagen binding protein domains ... More
Microfluidic, marker-free isolation of circulating tumor cells from blood samples.
Authors
JournalNat Protoc
PubMed ID24577360
Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
AuthorsPalomino-Segura M, Perez L, Farsakoglu Y, Virgilio T, Latino I, D'Antuono R, Chatziandreou N, Pizzagalli DU, Wang G, García-Sastre A, Sallusto F, Carroll MC, Neyrolles O, Gonzalez SF
JournalNat Microbiol
PubMed ID31358982
'The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system. Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after ... More
Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta.
AuthorsTang Y, Woodward BO, Pastor L, George AM, Petrechko O, Nouvet FJ, Haas DW, Jiang G, Hildreth JEK
JournalCell Rep
PubMed ID32234485
'Radical cure of HIV-1 (HIV) is hampered by the establishment of HIV reservoirs and persistent infection in deep tissues despite suppressive antiretroviral therapy (ART). Here, we show that among HIV-positive women receiving suppressive ART, cells from placental tissues including trophoblasts contain HIV RNA and DNA. These viruses can be reactivated ... More
Sensing of HIV-1 by TLR8 activates human T cells and reverses latency.
AuthorsMeås HZ, Haug M, Beckwith MS, Louet C, Ryan L, Hu Z, Landskron J, Nordbø SA, Taskén K, Yin H, Damås JK, Flo TH
JournalNat Commun
PubMed ID31919342
'During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well ... More
Detection and prognostic role of heterogeneous populations of melanoma circulating tumour cells.
AuthorsAya-Bonilla CA, Morici M, Hong X, McEvoy AC, Sullivan RJ, Freeman J, Calapre L, Khattak MA, Meniawy T, Millward M, Ziman M, Gray ES
JournalBr J Cancer
PubMed ID32037400
'Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application.' ... More
High-endothelial cell-derived S1P regulates dendritic cell localization and vascular integrity in the lymph node.
AuthorsSimmons S, Sasaki N, Umemoto E, Uchida Y, Fukuhara S, Kitazawa Y, Okudaira M, Inoue A, Tohya K, Aoi K, Aoki J, Mochizuki N, Matsuno K, Takeda K, Miyasaka M, Ishii M
JournalElife
PubMed ID31570118
'While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1-activation also occurs in vascular endothelial cells (ECs), including those of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1-G' ... More
The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation.
Authors
JournalBiomaterials
PubMed ID24974008
RCAN1.4 regulates VEGFR-2 internalisation, cell polarity and migration in human microvascular endothelial cells.
Authors
JournalAngiogenesis
PubMed ID28271280
Modeling expression ranks for noise-tolerant differential expression analysis of scRNA-seq data.
Authors
JournalGenome Res
PubMed ID33674351
Matrix metalloproteinase (MMP)-degradable tissue engineered periosteum coordinates allograft healing via early stage recruitment and support of host neurovasculature.
Authors
JournalBiomaterials
PubMed ID33271450
Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction.
Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing.
AuthorsSaraswati S, Marrow SMW, Watch LA, Young PP
JournalNat Commun
PubMed ID31289275
Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express ... More
High-Affinity Bent ß
AuthorsFan Z, Kiosses WB, Sun H, Orecchioni M, Ghosheh Y, Zajonc DM, Arnaout MA, Gutierrez E, Groisman A, Ginsberg MH, Ley K
JournalCell Rep
PubMed ID30605669
Leukocyte adhesion requires ß
GPR31-dependent dendrite protrusion of intestinal CX3CR1
AuthorsMorita N, Umemoto E, Fujita S, Hayashi A, Kikuta J, Kimura I, Haneda T, Imai T, Inoue A, Mimuro H, Maeda Y, Kayama H, Okumura R, Aoki J, Okada N, Kida T, Ishii M, Nabeshima R, Takeda K
JournalNature
PubMed ID30675063
Small intestinal mononuclear cells that express CX3CR1 (CX3CR1
Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells.
AuthorsSarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, Tran CM, Chu CR, Horvath S, Qi LS, Bhutani N, Rando TA, Sebastiano V
JournalNat Commun
PubMed ID32210226
Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can ... More
Co-culture of induced pluripotent stem cells with cardiomyocytes is sufficient to promote their differentiation into cardiomyocytes.
AuthorsChu AJ, Zhao EJ, Chiao M, Lim CJ
JournalPLoS One
PubMed ID32243463
Various types of stem cells and non-stem cells have been shown to differentiate or transdifferentiate into cardiomyocytes by way of co-culture with appropriate inducer cells. However, there is a limited demonstration of a co-culture induction system utilizing stem cell-derived cardiomyocytes as a stimulatory source for cardiac reprogramming (of stem cells ... More
A Platform for Studying of the Three-Dimensional Migration of Hematopoietic Stem/Progenitor Cells.
AuthorsLee E, Kim J, Kang Y, Shin JW
JournalTissue Eng Regen Med
PubMed ID32002840
Hematopoietic stem/progenitor cells (HSPCs) have the property to return to the bone marrow, which is believed to be critical in situations such as HSPC transplantation. This property plays an important role in the stemness, viability, and proliferation of HSPCs, also. However, most in vitro models so far have not sufficiently ... More
C3a elicits unique migratory responses in immature low-density neutrophils.
AuthorsHsu BE, Roy J, Mouhanna J, Rayes RF, Ramsay L, Tabariès S, Annis MG, Watson IR, Spicer JD, Costantino S, Siegel PM
JournalOncogene
PubMed ID32020055
Neutrophils represent the immune system's first line of defense and are rapidly recruited into inflamed tissue. In cancer associated inflammation, phenotypic heterogeneity has been ascribed to this cell type, whereby neutrophils can manifest anti- or pro-metastatic functions depending on the cellular/micro-environmental context. Here, we demonstrate that pro-metastatic immature low-density neutrophils ... More
Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.
AuthorsVoloshin T, Kaynan N, Davidi S, Porat Y, Shteingauz A, Schneiderman RS, Zeevi E, Munster M, Blat R, Tempel Brami C, Cahal S, Itzhaki A, Giladi M, Kirson ED, Weinberg U, Kinzel A, Palti Y
JournalCancer Immunol Immunother
PubMed ID32144446
Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, ... More
Inhibition of miR30a-3p by sulforaphane enhances gap junction intercellular communication in pancreatic cancer.
AuthorsGeorgikou C, Yin L, Gladkich J, Xiao X, Sticht C, Torre C, Gretz N, Gross W, Schäfer M, Karakhanova S, Herr I
JournalCancer Lett
PubMed ID31678166
The therapy resistance of pancreatic cancer is associated with the loss of gap junction intercellular communication and connexin 43 expression. The broccoli isothiocyanate sulforaphane restored these features and therapy sensitivity. We investigated whether microRNA signaling is involved. Established cell lines and a patient tissue array (n?=?96) were evaluated by miRNA ... More