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hepatocyte differentiation

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https://www.readbyqxmd.com/read/29786556/assessment-of-stem-cell-differentiation-based-on-genome-wide-expression-profiles
#1
REVIEW
Patricio Godoy, Wolfgang Schmidt-Heck, Birte Hellwig, Patrick Nell, David Feuerborn, Jörg Rahnenführer, Kathrin Kattler, Jörn Walter, Nils Blüthgen, Jan G Hengstler
In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786554/a-human-ipsc-line-capable-of-differentiating-into-functional-macrophages-expressing-zsgreen-a-tool-for-the-study-and-in-vivo-tracking-of-therapeutic-cells
#2
Martha Lopez-Yrigoyen, Antonella Fidanza, Luca Cassetta, Richard A Axton, A Helen Taylor, Jose Meseguer-Ripolles, Anestis Tsakiridis, Valerie Wilson, David C Hay, Jeffrey W Pollard, Lesley M Forrester
We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29778232/nuclear-bap1-loss-is-common-in-intrahepatic-cholangiocarcinoma-and-a-subtype-of-hepatocellular-carcinoma-but-rare-in-pancreatic-ductal-adenocarcinoma
#3
Asmaa Mosbeh, Khalil Halfawy, Wael S Abdel-Mageed, Dina Sweed, Mohamed H Abdel Rahman
Deletion in the 3p21 region, the chromosomal location of BAP1, has been reported in a subset of hepatocellular carcinoma (HCC), biliary and pancreatic cancers. This suggests that BAP1 could play a role in the pathogenesis of these tumors. We assessed the frequency of BAP1 loss by immunohistochemistry in 103 hepatic, biliary and pancreatic cancers. We also assessed chromosomal alterations in the BAP1 region in the same tumors by genotyping. We identified high frequency 4/8 (50%) of BAP1 loss in intrahepatic cholangicarcinoma (ICC)...
August 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29774067/estrogen-receptors-orchestrate-cell-growth-and-differentiation-to-facilitate-liver-regeneration
#4
Ta-Lun Kao, Yu-Ping Kuan, Wei-Chung Cheng, Wei-Chun Chang, Long-Bin Jeng, Shuyuan Yeh, Wen-Lung Ma
Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships...
2018: Theranostics
https://www.readbyqxmd.com/read/29763649/differentiation-of-umbilical-cord-derived-mesenchymal-stem-cells-to-hepatocyte-cells-by-transfection-of-mir-106a-mir-574-3p-and-mir-451
#5
Maryam Khosravi, Negar Azarpira, Sara Shamdani, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Studying the profile of micro RNAs (miRs) elucidated the highest expressed miRs in hepatic differentiation. In this study, we investigated to clarify the role of three embryonic overexpressed miRs (miR-106a, miR-574-3p and miR-451) during hepatic differentiation of human umbilical cord derived mesenchymal stem cells (UC-MSCs). We furthermore, aimed to explore whether overexpression of any of these miRs alone is sufficient to induce the differentiation of the UC-MSCs into hepatocyte-like cells. UC-MSCs were transfected either alone or together with miR-106a, miR-574-3p and miR-451 and their potential hepatic differentiation and alteration in gene expression profile, morphological changes and albumin secretion ability were investigated...
May 12, 2018: Gene
https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#6
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29759938/differentiation-therapy-by-epigenetic-reconditioning-exerts-antitumor-effects-on-liver-cancer-cells
#7
Luc Gailhouste, Lee Chuen Liew, Ken Yasukawa, Izuho Hatada, Yasuhito Tanaka, Hitoshi Nakagama, Takahiro Ochiya
Primary liver tumors are mainly represented by hepatocellular carcinoma (HCC), one of the most aggressive and resistant forms of cancer. Liver tumorigenesis is characterized by an accumulation of epigenetic abnormalities, leading to gene extinction and loss of hepatocyte differentiation. The aim of this work was to investigate the feasibility of converting liver cancer cells toward a less aggressive and differentiated phenotype using a process called epigenetic reconditioning. Here, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine (5-AZA) promoted an anti-cancer response by inhibiting HCC cell tumorigenicity...
April 26, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29752288/comparison-of-hepatic-nrf2-and-ahr-binding-in-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-treated-mice-demonstrates-nrf2-independent-pkm2-induction
#8
Rance Nault, Claire M Doskey, Kelly A Fader, Cheryl E Rockwell, Timothy R Zacharewski
2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) induces hepatic oxidative stress following activation of the aryl hydrocarbon receptor (AhR). Our recent studies showed TCDD induced pyruvate kinase muscle isoform 2 ( Pkm2 ) as a novel antioxidant response in normal differentiated hepatocytes. To investigate cooperative regulation between nuclear factor, erythroid derived 2, like 2 ( Nrf2 ) and the AhR in the induction of Pkm2 , hepatic ChIP-seq analyses were integrated with RNA-seq time course data from mice treated with TCDD for 2 - 168h...
May 11, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29750821/generation-of-hepatocyte-and-endocrine-pancreatic-like-cells-from-human-induced-endodermal-progenitor-cells
#9
Rangarajan Sambathkumar, Renate Akkerman, Sumitava Dastidar, Philip Roelandt, Manoj Kumar, Manmohan Bajaj, Ana Rita Mestre Rosa, Nicky Helsen, Veerle Vanslembrouck, Eric Kalo, Satish Khurana, Jos Laureys, Conny Gysemans, Marijke M Faas, Paul de Vos, Catherine M Verfaillie
Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14 transcription factors (TFs) in reprogramming MAPCs to induced endodermal progenitor cells (iENDO cells), defined as cells that can be long-term expanded and differentiated to both hepatocyte- and endocrine pancreatic-like cells...
2018: PloS One
https://www.readbyqxmd.com/read/29746655/downregulated-angiopoietin-like-peptide-8-production-at-calving-related-to-changes-in-lipid-metabolism-in-dairy-cows
#10
Misato Nakano, Yutaka Suzuki, Satoshi Haga, Eri Yamauchi, Dahye Kim, Koki Nishihara, K Nakajima, Takafumi Gotoh, Seungju Park, Myunggi Baik, Kazuo Katoh, Sanggun Roh
Acute physiological adaptation of lipid metabolism during the postpartum transition period of cows facilitates peripheral metabolic regulation. Hepatokines, which are hormones secreted from hepatocytes, are presumed to play a critical role in systemic metabolic regulation. Angiopoietin-like protein 8 (ANGPTL8) has been identified as a novel hepatokine associated with circulating triglyceride concentrations in mice and humans. However, regulation of ANGPTL8 and its physiological effects are still unknown in cattle...
May 9, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29743440/hepatic-histopathological-changes-and-dysfunction-in-primates-following-exposure-to-organic-arsenic-diphenylarsinic-acid
#11
Tomoyuki Masuda, Kazuhiro Ishii, Yukio Morishita, Nobuaki Iwasaki, Yasuyuki Shibata, Akira Tamaoka
Organic arsenic diphenylarsinic acid (DPAA[V]) accumulates at high concentrations in the liver of primates after its subchronic administration. However, no studies on the hepatic effects of organic arsenic compounds, including DPAA(V), on primates have been reported to date. To clarify the toxicokinetics of DPAA(V) in the liver of primates, hepatic tissue specimens were collected from cynomolgus monkeys (n = 32) at 5, 29, 170, and 339 days after repeated administration of DPAA(V) for 28 days. Four histopathological changes in the specimens were observed and pathologically evaluated...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29742288/metastatic-breast-cancer-to-the-liver-with-hepatoid-features-and-hep-par-1-antibody-positive-mimicking-hepatocellular-carcinoma
#12
Authur Affleck, William B Lyman, W Carl Jacobs, Chad A Livasy, John B Martinie, David A Iannitti, Dionisios Vrochides
The hepatocyte paraffin 1 antibody (Hep Par 1) has a high positive predictive value for differentiating hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma.1 We report a case of metastatic breast cancer to the liver with hepatoid histology and strong positive staining for Hep Par 1 mimicking hepatocellular carcinoma. To our knowledge, primary breast carcinoma staining Hep Par 1 positive has not been reported in the setting of hepatic metastasis. This article is protected by copyright. All rights reserved...
May 9, 2018: Histopathology
https://www.readbyqxmd.com/read/29735435/-tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-balance-liver-stem-cell-differentiation-in-cholestatic-cirrhosis
#13
Bo Yang, Qing Luo, Quan Kang, Jian Wang, Cheng Xiao, Zhi-Peng Li, Meng-Jia Gong, Yang Bi
OBJECTIVE: To investigate the changes of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1 ) in mice with cholestatic cirrhosis and their role in regulating the balance of liver stem cell differentiation. METHODS: Balb/c mice were subjected to bile duct ligation (BDL), and serum biochemical parameters were measured and hepatic histopathology was observed using HE staining to evaluate the modeling of cholestatic cirrhosis. Immunohistochemistry and Western blotting were used to detect the changes of TNF-α and TGF-β1 in the mice after modeling...
April 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29732151/fetal-hepatocyte-derived-culture-medium-elicits-adipocyte-differentiation-to-bile-duct-cell-lineages-in-a-mouse-model
#14
Hisataka Ogawa, Masamitsu Konno, Koichi Kawamoto, Naohiro Nishida, Jun Koseki, Tsunekazu Mizushima, Taroh Satoh, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Fetal cells in the developmental stages function with a distinct mechanism in comparison to adult tissues, which may be a useful source for regenerative medicine in postnatal medicine; however, the precise molecular mechanism remains to be elucidated fully. The present study investigated murine fetal hepatocytes, which were cultured in vitro , and the supernatants were used for the culture with murine adipose tissue-derived cells. Notably, the results indicated that fetal hepatocyte-derived culture medium elicits the induction of differentiation of adipose tissue-derived cells to bile duct cell lineages, but not to hepatocyte lineages in mice...
May 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29721169/differentiation-inducing-therapeutic-effect-of-notch-inhibition-in-reversing-malignant-transformation-of-liver-normal-stem-cells-via-met
#15
Hao Luo, Wei-Hui Liu, Hong-Yin Liang, Hong-Tao Yan, Ning Lin, Dong-Yu Li, Tao Wang, Li-Jun Tang
Background: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720662/de-novo-formation-of-the-biliary-system-by-tgf%C3%AE-mediated-hepatocyte-transdifferentiation
#16
Johanna R Schaub, Kari A Huppert, Simone N T Kurial, Bernadette Y Hsu, Ashley E Cast, Bryan Donnelly, Rebekah A Karns, Feng Chen, Milad Rezvani, Hubert Y Luu, Aras N Mattis, Anne-Laure Rougemont, Philip Rosenthal, Stacey S Huppert, Holger Willenbring
Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche 1 . Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS) 2 ...
May 2, 2018: Nature
https://www.readbyqxmd.com/read/29719629/improvement-of-non-alcoholic-steatohepatitis-by-hepatocyte-like-cells-generated-from-ipscs-with-oct4-sox2-klf4-parp1
#17
Yueh Chien, Chi-Shuan Huang, Hsin-Chi Lin, Kai-Hsi Lu, Ping-Hsing Tsai, Ying-Hsiu Lai, Kuan-Hsuan Chen, Shou-Dong Lee, Yi-Hsiang Huang, Chien-Ying Wang
The prevalence of nonalcoholic fatty liver disease (NAFLD) is usually increased with age. Non-alcoholic steatohepatitis (NASH), a serious form of NAFLD, may lead to cirrhosis and end-stage liver diseases. Induced pluripotent stem cells (iPSCs) hold promising potential in personalized medicine. Although obviation of c-Myc reduces tumorigenic risk, it also largely reduced the generation of iPSCs. Recently, Poly(ADP-ribose) polymerase 1 (Parp1) has been reported to enhance cell reprogramming. In this study, we demonstrated that forced expression of Oct4/Sox2/Klf4/Parp1 (OSKP) effectively promoted iPSC generation from senescent somatic cells from 18-month-old mouse...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719266/autologous-and-heterologous-cell-therapy-for-hemophilia-b-toward-functional-restoration-of-factor-ix
#18
Suvasini Ramaswamy, Nina Tonnu, Tushar Menon, Benjamin M Lewis, Kevin T Green, Derek Wampler, Paul E Monahan, Inder M Verma
Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreserved, cadaveric human hepatocytes remain functional for more than a year and secrete FIX at therapeutic levels. Hepatocytes from different sources (companies and donors) perform comparably in curing the bleeding defect. We also generated induced pluripotent stem cells (iPSCs) from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal)...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29709217/glycogenic-hepatopathy
#19
Johad Khoury, Yaniv Zohar, Naim Shehadeh, Tarek Saadi
BACKGROUND: Glycogenic hepatopathy (GH) is a disorder associated with uncontrolled diabetes mellitus, most commonly type 1, expressed as right upper quadrant abdominal pain, hepatomegaly and increased liver enzymes. The diagnosis may be difficult, because laboratory and imaging tests are not pathognomonic. Although GH may be suggested based on clinical presentation and imaging studies, the gold standard for diagnosis is a liver biopsy, showing a significant accumulation of glycogen within the hepatocytes...
April 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/29707971/human-multilineage-differentiating-stress-enduring-cells-exert-pleiotropic-effects-to-ameliorate-acute-lung-ischemia-reperfusion-injury-in-a-rat-model
#20
Hiroshi Yabuki, Shohei Wakao, Yoshihiro Kushida, Mari Dezawa, Yoshinori Okada
Posttransplantation lung ischemia-reperfusion (IR) injuries affect both patient survival and graft function. In this study, we evaluated the protective effects of infused human multilineage-differentiating stress-enduring (Muse) cells, a novel, easily harvested type of nontumorigenic endogenous reparative stem cell, against acute IR lung injury in a rat model. After a 2-h warm IR injury induction in a left rat lung, human Muse cells, human mesenchymal stem cells (MSCs), and vehicle were injected via the left pulmonary artery after reperfusion...
January 1, 2018: Cell Transplantation
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