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https://www.readbyqxmd.com/read/27898587/maternal-epigenetics-and-fetal-and-neonatal-growth
#1
Sofia Kitsiou-Tzeli, Maria Tzetis
PURPOSE OF REVIEW: The article provides an update on new insights of factors altering inherited maternal epigenome that ultimately affect fetal and neonatal growth. RECENT FINDINGS: A number of new publications have identified mechanisms through which maternal nutrition, environmental exposures such as stress and toxic substances altering expression of imprinted genes during pregnancy can influence fetal and neonatal phenotype and susceptibility to disease development later in life...
November 24, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27887572/maternal-smoking-impacts-key-biological-pathways-in-newborns-through-epigenetic-modification-in-utero
#2
Daniel M Rotroff, Bonnie R Joubert, Skylar W Marvel, Siri E Håberg, Michael C Wu, Roy M Nilsen, Per M Ueland, Wenche Nystad, Stephanie J London, Alison Motsinger-Reif
BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine...
November 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#3
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27820734/the-role-of-the-transcriptional-repressor-growth-factor-independent-1-in-the-formation-of-myeloid-cells
#4
Jennifer Fraszczak, Tarik Möröy
PURPOSE OF REVIEW: Growth factor independent 1 (Gfi1) is a transcriptional repressor that plays multiple roles during myeloid commitment and development. Gfi1-deficient mice lack granulocytes, accumulate aberrant monocytes and show a hyperactivity of macrophages toward bacterial cell wall components. Since these initial findings, numerous additional studies have confirmed the role of Gfi1 in myeloid differentiation from hematopoietic stem cells and multipotent progenitors to bipotential lymphoid/myeloid precursors and myeloid effector cells...
January 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27751776/atoh1-in-sensory-hair-cell-development-constraints-and-cofactors
#5
Aida Costa, Lynn M Powell, Sally Lowell, Andrew P Jarman
The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum...
October 14, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27677632/sudden-infant-death-syndrome-exposure-to-cigarette-smoke-leads-to-hypomethylation-upstream-of-the-growth-factor-independent-1-gfi1-gene-promoter
#6
Kristina Schwender, Hannah Holtkötter, Kristina Schulze Johann, Alina Glaub, Marianne Schürenkamp, Ulla Sibbing, Sabrina Banken, Mechtild Vennemann, Heidi Pfeiffer, Marielle Vennemann
PURPOSE: Smoking during pregnancy has long been known as an important risk factor for sudden infant death syndrome (SIDS). However, the precise relationship between the smoking behavior of the mother and SIDS still remains unclear. In this study, the influence of prenatal smoking exposure on the childrens' DNA methylation state of a CpG island located upstream of the promoter of the growth factor independent 1 (GFI1) gene was analyzed. METHODS: Blood samples of well-defined SIDS cases with non-smoking mothers (n = 11), SIDS cases with smoking mothers during pregnancy (n = 11), and non-SIDS cases (n = 6) were obtained from a previous study and methylation states were determined by bisulfite sequencing...
September 27, 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/27600904/the-transcriptional-repressor-gfi1-prevents-lupus-autoimmunity-by-restraining-tlr7-signaling
#7
Benoit Desnues, Amanda B Macedo, Diana Ordoñez-Rueda, Annie Roussel-Queval, Bernard Malissen, Pierre Bruhns, Marie Malissen, Lena Alexopoulou
The transcriptional repressor growth factor independence 1 (Gfi1) is important in myeloid and lymphoid differentiation. In the current study we evaluated the involvement of Gfi1 in systemic lupus erythematosus (SLE). We found that Genista mice, which carry a hypomorphic mutation in the gfi1 gene or Gfi1-deficient (Gfi1(-/-) ) mice develop signs of spontaneous lupus autoimmunity, including increased serum levels of IgM and IgG2a, autoantibodies against RNA and DNA, glomerular immunodeposits and increased frequencies of plasmablasts, germinal center (GC) B cells and age-associated B cells (ABCs)...
September 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27592349/the-promoter-and-multiple-enhancers-of-the-pou4f3-gene-regulate-expression-in-inner-ear-hair-cells
#8
Masatsugu Masuda, Yan Li, Kwang Pak, Eduardo Chavez, Lina Mullen, Allen F Ryan
Few enhancers that target gene expression to inner ear hair cells (HCs) have been identified. Using transgenic analysis of enhanced green fluorescent protein (eGFP) reporter constructs and bioinformatics, we evaluated the control of pou4f3 gene expression, since it is expressed only in HCs within the inner ear and continues to be expressed throughout life. An 8.5-kb genomic DNA fragment 5' to the start codon, containing three regions of high cross-species homology, drove expression in all embryonic and neonatal HCs, and adult vestibular and inner HCs, but not adult outer HCs...
September 3, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27580035/single-cell-analysis-of-mixed-lineage-states-leading-to-a-binary-cell-fate-choice
#9
Andre Olsson, Meenakshi Venkatasubramanian, Viren K Chaudhri, Bruce J Aronow, Nathan Salomonis, Harinder Singh, H Leighton Grimes
Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators. Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level...
August 31, 2016: Nature
https://www.readbyqxmd.com/read/27576864/dissecting-the-pre-placodal-transcriptome-to-reveal-presumptive-direct-targets-of-six1-and-eya1-in-cranial-placodes
#10
Nick Riddiford, Gerhard Schlosser
The pre-placodal ectoderm, marked by the expression of the transcription factor Six1 and its co-activator Eya1, develops into placodes and ultimately into many cranial sensory organs and ganglia. Using RNA-Seq in Xenopus laevis we screened for presumptive direct placodal target genes of Six1 and Eya1 by overexpressing hormone-inducible constructs of Six1 and Eya1 in pre-placodal explants, and blocking protein synthesis before hormone-inducing nuclear translocation of Six1 or Eya1. Comparing the transcriptome of explants with non-induced controls, we identified hundreds of novel Six1/Eya1 target genes with potentially important roles for placode development...
August 31, 2016: ELife
https://www.readbyqxmd.com/read/27500495/brpf1-is-essential-for-development-of-fetal-hematopoietic-stem-cells
#11
Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27493699/tobacco-smoking-differently-influences-cell-types-of-the-innate-and-adaptive-immune-system-indications-from-cpg-site-methylation
#12
Mario Bauer, Beate Fink, Loreen Thürmann, Markus Eszlinger, Gunda Herberth, Irina Lehmann
BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. RESULTS: Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86...
2015: Clinical Epigenetics
https://www.readbyqxmd.com/read/27467586/threshold-levels-of-gfi1-maintain-e2a-activity-for-b-cell-commitment-via-repression-of-id1
#13
Jennifer Fraszczak, Anne Helness, Riyan Chen, Charles Vadnais, François Robert, Cyrus Khandanpour, Tarik Möröy
A regulatory circuit that controls myeloid versus B lymphoid cell fate in hematopoietic progenitors has been proposed, in which a network of the transcription factors Egr1/2, Nab, Gfi1 and PU.1 forms the core element. Here we show that a direct link between Gfi1, the transcription factor E2A and its inhibitor Id1 is a critical element of this regulatory circuit. Our data suggest that a certain threshold of Gfi1 is required to gauge E2A activity by adjusting levels of Id1 in multipotent progenitors, which are the first bipotential myeloid/lymphoid-restricted progeny of hematopoietic stem cells...
2016: PloS One
https://www.readbyqxmd.com/read/27432513/a-gene-trap-transposon-eliminates-haematopoietic-expression-of-zebrafish-gfi1aa-but-does-not-interfere-with-haematopoiesis
#14
Roshana Thambyrajah, Deniz Ucanok, Maryam Jalali, Yasmin Hough, Robert Neil Wilkinson, Kathryn McMahon, Chris Moore, Martin Gering
A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity...
September 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27403598/genetic-contribution-to-variation-in-dna-methylation-at-maternal-smoking-sensitive-loci-in-exposed-neonates
#15
Semira Gonseth, Adam J de Smith, Ritu Roy, Mi Zhou, Seung-Tae Lee, Xiaorong Shao, Juhi Ohja, Margaret R Wrensch, Kyle M Walsh, Catherine Metayer, Joseph L Wiemels
Epigenome-wide DNA methylation association studies have identified highly replicable genomic loci sensitive to maternal smoking during gestation. The role of inter-individual genetic variation in influencing DNA methylation, leading to the possibility of confounding or bias of such associations, has not been assessed. We investigated whether the DNA methylation levels at the top 10 CpG sites previously associated with exposure to maternal smoking during gestation were associated with individual genetic variation at the genome-wide level...
July 12, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27399214/new-insights-into-the-regulation-by-runx1-and-gfi1-s-proteins-of-the-endothelial-to-hematopoietic-transition-generating-primordial-hematopoietic-cells
#16
Roshana Thambyrajah, Rahima Patel, Milena Mazan, Michael Lie-A-Ling, Andrew J Lilly, Alexia Eliades, Sara Menegatti, Eva Garcia-Alegria, Magdalena Florkowska, Kiran Batta, Valerie Kouskoff, Georges Lacaud
The first hematopoietic cells are generated very early in ontogeny to support the growth of the embryo and to provide the foundation to the adult hematopoietic system. There is a considerable therapeutic interest in understanding how these first blood cells are generated in order to try to reproduce this process in vitro. This would allow to generate at will blood products or hematopoietic cell populations from embryonic stem cells (ESCs), induced pluripotent stem cells or through directed reprogramming. Recent studies have clearly established that the first hematopoietic cells originate from a hemogenic endothelium (HE) through an endothelial to hematopoietic transition (EHT)...
July 11, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27371613/differing-expression-profiles-of-notch-enterocyte-and-wnt-secretory-lineage-signallings-are-associated-with-morphological-diversity-of-appendiceal-tumours
#17
Xianyong Gui, Ziran Meng, Yarrow J McConnell, Shuhong Liu, Vincent G Falck, Lloyd A Mack, Walley J Temple
BACKGROUND: Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by Notch-Hes1 pathway, while secretory lineage is driven by Wnt-Math1 pathway and further separated by different downstream signallings into three sublineages (Gfi1-Klf4/Elf3 for goblet cells, Gfi1-Sox9 for Paneth cells and Ngn3-Pdx1/Beta2/Pax4 for enteroendocrine cells)...
July 1, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27324145/embryonic-intra-aortic-clusters-undergo-myeloid-differentiation-mediated-by-mesonephros-derived-csf1-in-mouse
#18
Tatsuya Sasaki, Yuka Tanaka, Kasem Kulkeaw, Ayako Yumine-Takai, Keai Sinn Tan, Ryuichi Nishinakamura, Junji Ishida, Akiyoshi Fukamizu, Daisuke Sugiyama
The aorta-gonad-mesonephros (AGM) region contains intra-aortic clusters (IACs) thought to have acquired hematopoietic stem cell (HSC) potential in vertebrate embryos. To assess extrinsic regulation of IACs in the AGM region, we employed mouse embryos harboring a Sall1-GFP reporter gene, which allows identification of mesonephros cells based on GFP expression. Analysis of AGM region tissue sections confirmed mesonephros GFP expression. Mesonephric cells sorted at E10.5 expressed mRNA encoding Csf1, a hematopoietic cytokine, and corresponding protein, based on real-time PCR and immunocytochemistry, respectively...
October 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27284976/the-transcriptional-repressor-gfi1-plays-a-critical-role-in-the-development-of-nkt1-and-nkt2-type-inkt-cells
#19
Toshiaki Yasuoka, Makoto Kuwahara, Takeshi Yamada, Saho Maruyama, Junpei Suzuki, Masaru Taniguchi, Masaki Yasukawa, Masakatsu Yamashita
Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of Gfi1-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific Gfi1-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1pos iNKT cells was significantly reduced. Furthermore, CD4pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific Gfi1-deficient mice...
2016: PloS One
https://www.readbyqxmd.com/read/27283242/ampk-promotes-osteogenesis-and-inhibits-adipogenesis-through-ampk-gfi1-opn-axis
#20
Yu-Gang Wang, Xin-Hua Qu, Ying Yang, Xiu-Guo Han, Lei Wang, Han Qiao, Qi-Ming Fan, Ting-Ting Tang, Ke-Rong Dai
Several metabolic, genetic and oncogenic bone diseases share the common pathological phenotype of defective bone marrow stromal cell (BMSC) differentiation. Many reports in bone science in the past several years have suggested that the skeleton also has an endocrine role. The role of AMP-activated protein kinase (AMPK) as an energy metabolism sensor and how it regulates BMSC differentiation is largely unknown. In the current study, we used AMPK agonists to activate AMPK in MC3T3-E1 cells to investigate the functional roles of AMPK in osteogenesis...
September 2016: Cellular Signalling
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