Abstract:
:Among the multiple metabolic signals involved in the establishment of the hepatic zonation, oxygen could play a key role. Indeed, depending on hepatocyte position in the hepatic lobule, gene expression and metabolism are differently affected by the oxygen gradient present across the lobule. The aim of this study is to understand whether an oxygen gradient, generated in vitro in our developed device, is sufficient to instruct a functional metabolic zonation during the differentiation of human embryonic stem cells (hESCs) from endoderm toward terminally differentiated hepatocytes, thus mimicking the in vivo situation. For this purpose, a microfluidic device was designed for the generation of a stable oxygen gradient. The oxygen gradient was applied to differentiating hESCs at the pre-hepatoblast stage. The definitive endoderm and hepatic endoderm cells were characterized by the expression of the transcription factor SOX-17 and alpha-fetoprotein (AFP). Immature and mature hepatocytes were characterized by hepatocyte nuclear factor 4-alpha (HNF-4α) and albumin (ALB) expression and also analyzed for cytochrome P450 (CYP3A4) zonation and glycogen accumulation through PAS staining. Metabolic zonated genes expression was assessed through quantitative real time PCR. Application of the oxygen gradient during differentiation induced zonated glycogen storage, which was higher in the hepatocytes grown in high pO2 compared to those grown in low pO2. The mRNA levels of glutamine synthetase (GLUL), beta-catenin (CTNNB) and its direct target cyclin D1 (CCND1) showed significantly higher expression in the cells grown in low pO2 compared to those grown in high pO2. On the contrary, carbamoyl-phosphate synthetase 1 (CPS1), ALB, the proliferative marker ki67 (MKI67) and cyclin A (CCNA) resulted to be significantly higher expressed in cells cultured in high pO2 compared to those cultured in low pO2. These results indicate that the oxygen gradient generated in our device can instruct the establishment of a functional metabolic zonation in differentiating hESCs. The possibility to obtain differentiated hepatocytes in vitro may allow in the future to deepen our knowledge about the physiology/pathology of hepatocytes in relation to the oxygen content.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Tonon F,Giobbe GG,Zambon A,Luni C,Gagliano O,Floreani A,Grassi G,Elvassore Ndoi
10.1038/s41598-019-49412-6subject
Has Abstractpub_date
2019-09-19 00:00:00pages
13557issue
1issn
2045-2322pii
10.1038/s41598-019-49412-6journal_volume
9pub_type
杂志文章abstract::Surface hydrophobicity of silicon with sound durability under mechanical abrasion is highly desirable for practical needs. However, the reported micro-pyramid/nanowires structures suffer from the saturation characteristics of contact angle at around 132 degree, which impede the promotions toward reaching the state of ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-37853-4
更新日期:2019-02-07 00:00:00
abstract::Adipocytes are the prevalent stromal cell type in adult bone marrow (BM), and leukemia cells continuously adapt to deficiency of nutrients acquiring chemoresistant profiles in the BM microenvironment. We have previously shown that fatty acid metabolism is a key energy pathway for survival of acute myeloid leukemia (AM...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-35198-6
更新日期:2018-11-15 00:00:00
abstract::In this study, the influence of intratumoral morphological heterogeneity of breast cancer on neoadjuvant chemotherapy (NAC) efficiency was investigated. In particular, we analysed the association of NAC response and pre- and post-NAC expression of the main multidrug resistance (MDR) genes--ABCB1, ABCC1, ABCC5, ABCG1, ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep04709
更新日期:2014-04-16 00:00:00
abstract::Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M incre...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00636
更新日期:2012-01-01 00:00:00
abstract::Tumor necrosis factor (TNF) is best known for inducing a rapid but transient NF-κB-mediated inflammatory response. We investigated later phases of TNF signaling, after the initial transient induction of inflammatory genes has subsided, in primary human macrophages. TNF signaling induced expression of late response gen...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep31959
更新日期:2016-08-25 00:00:00
abstract::The controlled preparation of Au nanoparticles (NPs) in the size range of 6 to 22 nm is explored in this study. The Au NPs were prepared by the reduction of tetrachloroauric acid using maltose in the presence of nonionic surfactant Tween 80 at various concentrations to control the size of the resulting Au NPs. With in...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-22976-5
更新日期:2018-03-15 00:00:00
abstract::SIRT1, the NAD+-dependent protein deacetylase, controls cell-cycle progression and apoptosis by suppressing p53 tumour suppressor. Although SIRT1 is known to be phosphorylated by JNK1 upon oxidative stress and subsequently down-regulated, it still remains elusive how SIRT1 stability and activity are controlled. Here, ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37578
更新日期:2016-11-24 00:00:00
abstract::A polymer coating as polycaprolactone (PCL) is applied to improve the initial corrosion resistance of biodegradable magnesium. In addition, plasma electrolytic oxidation (PEO) is performed to increase adhesion between the polymer and the metal. However, when a complex-shaped material such as a screw is implanted in a ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-31359-9
更新日期:2018-09-05 00:00:00
abstract::Beta-glucans are a heterologous group of fibrous glucose polymers that are a major constituent of cell walls in Ascomycetes and Basidiomycetes fungi. Synthesis of β (1,3)- and (1,6)-glucans is coordinated with fungal cell growth and development, thus, is under tight genetic regulation. Here, we report that β-glucan sy...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10199
更新日期:2015-05-11 00:00:00
abstract::Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 60...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41002
更新日期:2017-02-01 00:00:00
abstract::A fast-growing stalagmite from the central California coast provides a high-resolution record of climatic changes synchronous with global perturbations resulting from the catastrophic drainage of proglacial Lake Agassiz at ca. 8.2 ka. High frequency, large amplitude variations in carbon isotopes during the 8.2 ka even...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04215-5
更新日期:2017-06-20 00:00:00
abstract::The accelerated discovery of disease-related genes emerging from genomic studies has strained the capacity of traditional genetically engineered mouse models (GEMMs) to provide in-vivo validation. Direct, somatic, genetic engineering approaches allow for accelerated and flexible genetic manipulation and represent an a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11061
更新日期:2015-06-05 00:00:00
abstract::Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crys...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19994
更新日期:2016-02-01 00:00:00
abstract::A low-bandgap acceptor (ITIC) was added to a binary system composed of a wide-bandgap polymer (PBT-OTT) and an acceptor (PC71BM) to increase the light harvesting efficiency of the associated organic solar cells (OSCs). A ternary blend OSC with an acceptor ratio of PC71BM:ITIC = 8:2 was found to exhibit a power convers...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48306-x
更新日期:2019-08-19 00:00:00
abstract::Skeletal muscle and adipose tissue play an important role in maintaining metabolic homeostasis and thermogenesis. We aimed to investigate the effects of single and repeated exposure to whole-body cryotherapy in volunteers with different physical fitness levels on 25-hydroxyvitamin D (25(OH)D) and myokines. The study i...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/s41598-020-63002-x
更新日期:2020-04-10 00:00:00
abstract::As the precious resource for quantum information processing, quantum coherence can be created remotely if the involved two sites are quantum correlated. It can be expected that the amount of coherence created should depend on the quantity of the shared quantum correlation, which is also a resource. Here, we establish ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34380
更新日期:2016-09-29 00:00:00
abstract::The majority of individuals with Down syndrome (DS) do not exhibit accurate accommodation, with the aetiology of this deficit unknown. This study examines the mechanism underlying hypoaccommodation in DS by simultaneously investigating the 'near triad' - accommodation, vergence and pupillary response. An objective pho...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20444
更新日期:2016-02-05 00:00:00
abstract::Transcranial focused ultrasound (US) has been demonstrated to stimulate neurons in animals and humans, but the mechanism of this effect is unknown. It has been hypothesized that US, a mechanical stimulus, may mediate cellular discharge by activating mechanosensitive ion channels embedded within cellular membranes. To ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24170
更新日期:2016-04-26 00:00:00
abstract::Cross-linked protein crystals (CLPCs) are very useful materials in applications such as biosensors, catalysis, and X-ray crystallography. Hence, preparation of CLPCs is an important research direction. During the preparation of CLPCs, an often encountered problem is that cracks may appear in the crystals, which may fi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep34770
更新日期:2016-10-05 00:00:00
abstract::Nanodiamonds containing high density ensembles of negatively charged nitrogen-vacancy (NV(-)) centers are promising fluorescent biomarkers due to their excellent photostability and biocompatibility. The NV(-) centers in the particles have a fluorescence lifetime of up to 20 ns, which distinctly differs from those (<10...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05574
更新日期:2014-07-04 00:00:00
abstract::Reconstructing diet is critical to understanding hominin adaptations. Isotopic and functional morphological analyses of early hominins are compatible with consumption of hard foods, such as mechanically-protected seeds, but dental microwear analyses are not. The protective shells surrounding seeds are thought to induc...
journal_title:Scientific reports
pub_type: 历史文章,杂志文章
doi:10.1038/s41598-019-57403-w
更新日期:2020-01-17 00:00:00
abstract::We experimentally investigate a discharging flux of granular particles through a sieve plate subject to vertical vibrations. The mean mass flux shows a non-monotonic relation with the vibration strength. High-speed photography reveals that two stages, the free flight of the particles' bulk over the plate and the adhes...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep09880
更新日期:2015-06-09 00:00:00
abstract::There is increasing demand for safe and effective sanitizers for irrigation water disinfection to prevent transmission of foodborne pathogens to fresh produce. Here we compared the efficacy of pH-neutral electrolyzed oxidizing water (EOW), sodium hypochlorite (NaClO) and chlorine dioxide (ClO2) against single and mixe...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-56248-7
更新日期:2019-12-27 00:00:00
abstract::Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inv...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-50323-9
更新日期:2019-09-25 00:00:00
abstract::In this work, Ni nanoparticles were directly decorated on graphene (G) nanosheets via mechanical ball milling. Based on transmission electron microscopy observations, the Ni nanoparticles were well dispersed and attached to the G nanosheet without any agglomerations. Electrochemical results showed that the capacitance...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32082
更新日期:2016-08-24 00:00:00
abstract::The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine wilt disease that has devastated pine forests in Asia. Parasitic nematodes are known to have evolved antioxidant stress responses that defend against host plant defenses. In this study, the infestation of whitebark pine, Pinus bungean, wit...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep27438
更新日期:2016-06-07 00:00:00
abstract::Mixed Plasmodium malaria infections can lead to severe malaria. This systematic review and meta-analysis aimed to explore the prevalence of severe mixed Plasmodium malaria infection and to compare it with the prevalence of severe P. falciparum malaria mono-infection across the included studies. Original English-langua...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-020-68082-3
更新日期:2020-07-06 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06311
更新日期:2014-09-09 00:00:00
abstract::The structural, electronic, transport and optical properties of black phosphorus/MoS2 (BP/MoS2) van der Waals (vdw) heterostructure are investigated by using first principles calculations. The band gap of BP/MoS2 bilayer decreases with the applied normal compressive strain and a semiconductor-to-metal transition is ob...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16448
更新日期:2015-11-10 00:00:00
abstract::Herein, we have fabricated rutile TiO2 nanorod-coupled α-Fe2O3 by a wet-chemical process. It is demonstrated that the visible activities for photoelectrochemical water oxidation and for degrading pollutant of α-Fe2O3 are greatly enhanced after coupling a proper amount of rutile nanorods. The enhanced activity is attri...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06180
更新日期:2014-08-26 00:00:00