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https://www.readbyqxmd.com/read/29353324/stromalized-microreactor-supports-murine-hematopoietic-progenitor-enrichment
#1
Danika Khong, Matthew Li, Amy Singleton, Ling-Yee Chin, Biju Parekkadan
There is an emerging need to process, expand, and even genetically engineer hematopoietic stem and progenitor cells (HSPCs) prior to administration for blood reconstitution therapy. A closed-system and automated solution for ex vivo HSC processing can improve adoption and standardize processing techniques. Here, we report a recirculating flow bioreactor where HSCs are stabilized and enriched for short-term processing by indirect fibroblast feeder coculture. Mouse 3 T3 fibroblasts were seeded on the extraluminal membrane surface of a hollow fiber micro-bioreactor and were found to support HSPC cell number compared to unsupported BMCs...
January 20, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29353058/chd7-is-critical-for-early-t-cell-development-and-thymus-organogenesis-in-zebrafish
#2
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353044/bmp4-signaling-in-npcs-upregulates-bcl-xl-to-promote-their-survival-in-the-presence-of-fgf-2
#3
Hanako Yamamoto, Masashi Kurachi, Masae Naruse, Koji Shibasaki, Yasuki Ishizaki
We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29352600/placental-control-of-metabolic-adaptations-in-the-mother-for-an-optimal-pregnancy-outcome-what-goes-wrong-in-gestational-diabetes
#4
David J Hill
As pregnancy progresses the placental syncytiotrophoblast increasingly assumes control of maternal glucose homeostasis through the release and counter-balancing effects of placental lactogen (PL) and placental variant growth hormone (GH-V). While local actions of these hormones on placental growth and function are likely to exist, each also exerts indirect actions to ensure fetal nutritional availability through modulation of the maternal insulin/insulin-like growth factor axis. Peripheral insulin resistance results from the increasing levels of GH-V in the maternal circulation and is counter-balanced by an increase in insulin availability through an expansion of maternal pancreatic β-cell mass...
January 9, 2018: Placenta
https://www.readbyqxmd.com/read/29352171/a-urine-dependent-human-urothelial-organoid-offers-a-potential-alternative-to-rodent-models-of-infection
#5
Harry Horsley, Dhanuson Dharmasena, James Malone-Lee, Jennifer L Rohn
Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#6
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352015/sox2-is-required-for-olfactory-pit-formation-and-olfactory-neurogenesis-through-bmp-restriction-and-hes5-upregulation
#7
Tamilarasan K Panaliappan, Walter Wittmann, Vijay K Jidigam, Sara Mercurio, Jessica A Bertolini, Soufien Sghari, Raj Bose, Cedric Patthey, Silvia K Nicolis, Lena Gunhaga
The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage...
January 19, 2018: Development
https://www.readbyqxmd.com/read/29351999/mll1-promotes-il-7-responsiveness-and-survival-during-b-cell-differentiation
#8
Tao Gan, Bin E Li, Bibhu P Mishra, Kenneth L Jones, Patricia Ernst
B lymphocyte differentiation is an exquisitely regulated homeostatic process resulting in continuous production of appropriately selected B cells. Relatively small changes in gene expression can result in deregulation of this process, leading to acute lymphocytic leukemia (ALL), immune deficiency, or autoimmunity. Translocation of MLL1 (KMT2A) often results in a pro-B cell ALL, but little is known about its role in normal B cell differentiation. Using a Rag1-cre mouse knock-in to selectively delete Mll1 in developing lymphocytes, we show that B cell, but not T cell, homeostasis depends on MLL1...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351627/repair-kinetics-of-dna-double-strand-breaks-and-incidence-of-apoptosis-in-mouse-neural-stem-progenitor-cells-and-their-differentiated-neurons-exposed-to-ionizing-radiation
#9
Hiroki Kashiwagi, Kazunori Shiraishi, Kenta Sakaguchi, Tomoya Nakahama, Seiji Kodama
Neuronal loss leads to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray-induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation...
January 17, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29351579/lack-of-methyl-cpg-binding-protein-2-mecp2-affects-cell-fate-refinement-during-embryonic-cortical-development
#10
Clementina Cobolli Gigli, Linda Scaramuzza, Marco De Simone, Riccardo L Rossi, Davide Pozzi, Massimiliano Pagani, Nicoletta Landsberger, Francesco Bedogni
During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo...
January 17, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29351489/cooperative-function-of-pdx1-and-oc1-in-multipotent-pancreatic-progenitors-impacts-postnatal-islet-maturation-and-adaptability
#11
Peter A Kropp, Jennifer C Dunn, Bethany A Carboneau, Doris A Stoffers, Maureen Gannon
The transcription factors Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors (MPCs), but their expression patterns diverge in hormone-expressing cells, with Oc1 expression being extinguished in the endocrine lineage and Pdx1 being maintained at high levels in β cells. We previously demonstrated that cooperative function of these two factors in MPCs is necessary for proper specification and differentiation of pancreatic endocrine cells. In those studies, we observed a persistent decrease in expression of the β-cell maturity factor MafA...
December 12, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#12
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29351056/remediation-of-radiation-induced-cognitive-dysfunction-through-oral-administration-of-the-neuroprotective-compound-nsi-189
#13
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29350973/epithelial-progenitor-cells-take-center-stage-in-lung-transplantation
#14
Natalia F Smirnova, Oliver Eickelberg
No abstract text is available yet for this article.
January 19, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29350342/mesenchymal-stromal-cells-of-the-bone-marrow-and-natural-killer-cells-cell-interactions-and-cross-modulation
#15
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent progenitor cells that have shown promise for several different therapeutic applications. As they are able to modulate the function of several types of immune cells, BM-MSCs are highly important in the field of cell-based immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is crucial for improving their therapeutic efficiency. Here, we observed that the type of NK cell-activating cytokine (e.g., IL-2, IL-12, IL-15 and IL-21) strongly influenced the outcomes of their interactions with BM-MSCs...
January 19, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29350308/the-ppar%C3%AE-agonist-efatutazone-delays-invasive-progression-and-induces-differentiation-of-ductal-carcinoma-in-situ
#16
Virginie Ory, William B Kietzman, Jacob Boeckelman, Bhaskar V Kallakury, Anton Wellstein, Priscilla A Furth, Anna T Riegel
PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression. METHODS: We utilized the high-affinity PPARγ agonist, efatutazone, to activate endogenous PPARγ in a well-defined model for the progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and 3D conditions...
January 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29350283/epigenetic-regulation-of-neuroblastoma-development
#17
REVIEW
Durinck Kaat, Speleman Frank
In recent years, technological advances have enabled a detailed landscaping of the epigenome and the mechanisms of epigenetic regulation that drive normal cell function, development and cancer. Rather than merely a structural entity to support genome compaction, we now look at chromatin as a very dynamic and essential constellation that is actively participating in the tight orchestration of transcriptional regulation as well as DNA replication and repair. The unique feature of chromatin flexibility enabling fast switches towards more or less restricted epigenetic cellular states is, not surprisingly, intimately connected to cancer development and treatment resistance, and the central role of epigenetic alterations in cancer is illustrated by the finding that up to 50% of all mutations across cancer entities affect proteins controlling the chromatin status...
January 19, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29349923/magnetic-macroporous-hydrogels-as-a-novel-approach-for-perfused-stem-cell-culture-in-3d-scaffolds-via-contactless-motion-control
#18
Lisa Rödling, Esther Magano Volz, Annamarija Raic, Katharina Brändle, Matthias Franzreb, Cornelia Lee-Thedieck
There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth-limiting metabolites. To overcome the diffusion-limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems...
January 19, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29348578/a-matter-of-life-and-death-stem-cell-survival-in-tissue-regeneration-and-tumour-formation
#19
REVIEW
Despina Soteriou, Yaron Fuchs
In recent years, great strides have been made in our understanding of how stem cells (SCs) govern tissue homeostasis and regeneration. The inherent longevity of SCs raises the possibility that the unique protective mechanisms in these cells might also be involved in tumorigenesis. In this Opinion article, we discuss how SCs are protected throughout their lifespan, focusing on quiescent behaviour, DNA damage response and programmed cell death. We briefly examine the roles of adult SCs and progenitors in tissue repair and tumorigenesis and explore how signals released from dying or dormant cells influence the function of healthy or aberrant SCs...
January 19, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29348537/radionuclides-transform-chemotherapeutics-into-phototherapeutics-for-precise-treatment-of-disseminated-cancer
#20
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
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