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Hematopoietic stem cell BMP

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https://www.readbyqxmd.com/read/29973374/mechanisms-in-endocrinology-bone-marrow-adiposity-and-bone-a-bad-romance
#1
Tareck Rharass, Stephanie Lucas
Bone marrow adipocytes (BMA) constitute an original and heterogeneous fat depot whose development appears interlinked with bone status throughout life. The gradual replacement of the hematopoietic tissue by BMA arises in a well-ordered way during childhood and adolescence concomitantly to bone growth and continues at a slower rate throughout the adult life. Importantly, BM adiposity quantity is found well associated with BMD (Bone Mineral Density) loss at different skeletal sites in primary osteoporosis such as in ageing or menopause but also in secondary osteoporosis consecutive to anorexia nervosa...
July 4, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29477370/the-bmp-pathway-a-unique-tool-to-decode-the-origin-and-progression-of-leukemia
#2
REVIEW
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SCs) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer, but its important properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cell (LSC) survival is responsible for disease persistence and drug resistance, probably due to their sustained interactions with the tumor niche. Bone morphogenetic protein (BMP) signaling is a key pathway controlling stem cells and their niche...
May 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29093060/a-molecular-roadmap-of-the-agm-region-reveals-bmper-as-a-novel-regulator-of-hsc-maturation
#3
Alison C McGarvey, Stanislav Rybtsov, Céline Souilhol, Sara Tamagno, Ritva Rice, David Hills, Duncan Godwin, David Rice, Simon R Tomlinson, Alexander Medvinsky
In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28852936/down-regulation-of-pax2-promotes-in-vitro-differentiation-of-podocytes-from-human-cd34-cells
#4
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Podocytes are major kidney cells that help in glomerular filtration and any damage or loss is a major event in the progression of kidney diseases. Understanding podocytes development will help in designing therapeutic strategies against these renal diseases. Therefore, in vitro generation of podocytes from adult hematopoietic CD34+ stem cells is explored in the present study. Apheretically, isolated human HSCs from peripheral blood showed the presence of CD34 surface glycoprotein through immunocytochemistry (ICC) and flowcytometry...
December 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28683563/modulation-of-hematopoietic-lineage-specification-impacts-trem2-expression-in-microglia-like-cells-derived-from-human-stem-cells
#5
Peter J Amos, Susan Fung, Amanda Case, Jerusalem Kifelew, Leah Osnis, Carole L Smith, Kevin Green, Alipi Naydenov, Macarena Aloi, Jesse J Hubbard, Aravind Ramakrishnan, Gwenn A Garden, Suman Jayadev
Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28584091/dissecting-bmp-signaling-input-into-the-gene-regulatory-networks-driving-specification-of-the-blood-stem-cell-lineage
#6
Arif Kirmizitas, Stuart Meiklejohn, Aldo Ciau-Uitz, Rachel Stephenson, Roger Patient
Hematopoietic stem cells (HSCs) that sustain lifelong blood production are created during embryogenesis. They emerge from a specialized endothelial population, termed hemogenic endothelium (HE), located in the ventral wall of the dorsal aorta (DA). In Xenopus , we have been studying the gene regulatory networks (GRNs) required for the formation of HSCs, and critically found that the hemogenic potential is defined at an earlier time point when precursors to the DA express hematopoietic as well as endothelial genes, in the definitive hemangioblasts (DHs)...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#7
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/27447537/thrombopoietin-induces-hematopoiesis-from-mouse-es-cells-via-hif-1%C3%AE-dependent-activation-of-a-bmp4-autoregulatory-loop
#8
Andri Pramono, Azadeh Zahabi, Tatsuya Morishima, Dan Lan, Karl Welte, Julia Skokowa
Understanding the molecular mechanisms underlying hematopoietic differentiation of embryonic stem (ES) cells may help to ascertain the conditions for the in vitro generation of hematopoietic cells. Previously, we found that patients with congenital amegakaryocytic thrombocytopenia (CAMT), who develop pancytopenia early after birth, harbor mutations within the thrombopoietin (TPO) receptor, c-MPL. This knowledge, together with observations in vitro and in vivo, suggests that TPO/c-MPL signaling promotes early hematopoiesis...
July 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27252436/a-validated-preclinical-animal-model-for-primary-bone-tumor-research
#9
Ferdinand Wagner, Boris M Holzapfel, Laure Thibaudeau, Melanie Straub, Ming-Tat Ling, Joachim Grifka, Daniela Loessner, Jean-Pierre Lévesque, Dietmar W Hutmacher
BACKGROUND: Despite the introduction of 21st-century surgical and neoadjuvant treatment modalities, survival of patients with osteosarcoma (OS) has not improved in two decades. Advances will depend in part on the development of clinically relevant and reliable animal models. This report describes the engineering and validation of a humanized tissue-engineered bone organ (hTEBO) for preclinical research on primary bone tumors in order to minimize false-positive and false-negative results due to interspecies differences in current xenograft models...
June 1, 2016: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/26966074/targeting-of-the-blt2-in-chronic-myeloid-leukemia-inhibits-leukemia-stem-progenitor-cell-function
#10
Meifang Xiao, Hongmei Ai, Tao Li, Pasupati Rajoria, Prakash Shahu, Xiansong Li
Imatinib, a tyrosine kinase inhibitor (TKI) has significantly improved clinical outcome for chronic myeloid leukemia (CML) patients. However, patients develop resistance when the disease progresses to the blast phase (BP) and the mechanisms are not well understood. Here we show that BCR-ABL activates BLT2 in hematopoietic stem/progenitor cells to promote leukemogenesis and this involves the p53 signaling pathway. Compared to normal bone marrow (NBM), the mRNA and protein levels of BLT2 are significantly increased in BP-CML CD34(+) stem/progenitor cells...
April 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26923823/bmp-and-hedgehog-regulate-distinct-agm-hematopoietic-stem-cells-ex%C3%A2-vivo
#11
Mihaela Crisan, Parham Solaimani Kartalaei, Alex Neagu, Sofia Karkanpouna, Tomoko Yamada-Inagawa, Caterina Purini, Chris S Vink, Reinier van der Linden, Wilfred van Ijcken, Susana M Chuva de Sousa Lopes, Rui Monteiro, Christine Mummery, Elaine Dzierzak
Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway...
March 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/26462358/-construction-and-identification-of-adenovirus-vector-expressing-bone-morphogenetic-protein-2-and-transforming-growth-factor-%C3%AE-3-genes-and-their-expression-in-bone-marrow-mesenchymal-stem-cells-of-diannan-small-ear-pigs
#12
Xin Wang, Yanlin Li, Yaofen Jin, Jianming Chen, Huijian Wang, Chuan He, Shuhai Cao, Fengkai Zhao
OBJECTIVE: To construct and identify the recombinant adenovirus vector expressing bone morphogenetic protein 2 (BMP-2) and transforming growth factor β3 (TGF-β3) genes, to observe the expressions of BMP-2 and TGF-β3 after transfected into bone marrow mesenchymal stem cells (BMSCs) of the Diannan small-ear pigs. METHODS: BMP-2 cDNA and TGF-β3 cDNA were amplified by PCR, and were subcloned into the pEC3.1 (+) plasmid to obtain pEC-GIE 3.1-BMP-2 and pEC-GIE3.1-TGF-β3 plasmid respectively...
July 2014: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/26282601/bmp-signalling-differentially-regulates-distinct-haematopoietic-stem-cell-types
#13
Mihaela Crisan, Parham Solaimani Kartalaei, Chris S Vink, Chris Vink, Tomoko Yamada-Inagawa, Karine Bollerot, Wilfred van IJcken, Reinier van der Linden, Susana M Chuva de Sousa Lopes, Rui Monteiro, Christine Mummery, Elaine Dzierzak
Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they are first generated in the aorta-gonad-mesonephros region, but at later developmental stages, its role in HSCs is controversial. Here we show that HSCs in murine fetal liver and the bone marrow are of two types that can be prospectively isolated--BMP activated and non-BMP activated...
2015: Nature Communications
https://www.readbyqxmd.com/read/26153229/inhibition-of-%C3%AE-catenin-signaling-respecifies-anterior-like-endothelium-into-beating-human-cardiomyocytes
#14
Nathan J Palpant, Lil Pabon, Meredith Roberts, Brandon Hadland, Daniel Jones, Christina Jones, Randall T Moon, Walter L Ruzzo, Irwin Bernstein, Ying Zheng, Charles E Murry
During vertebrate development, mesodermal fate choices are regulated by interactions between morphogens such as activin/nodal, BMPs and Wnt/β-catenin that define anterior-posterior patterning and specify downstream derivatives including cardiomyocyte, endothelial and hematopoietic cells. We used human embryonic stem cells to explore how these pathways control mesodermal fate choices in vitro. Varying doses of activin A and BMP4 to mimic cytokine gradient polarization in the anterior-posterior axis of the embryo led to differential activity of Wnt/β-catenin signaling and specified distinct anterior-like (high activin/low BMP) and posterior-like (low activin/high BMP) mesodermal populations...
September 15, 2015: Development
https://www.readbyqxmd.com/read/25870201/flow-induced-protein-kinase-a-creb-pathway-acts-via-bmp-signaling-to-promote-hsc-emergence
#15
Peter Geon Kim, Haruko Nakano, Partha P Das, Michael J Chen, R Grant Rowe, Stephanie S Chou, Samantha J Ross, Kathleen M Sakamoto, Leonard I Zon, Thorsten M Schlaeger, Stuart H Orkin, Atsushi Nakano, George Q Daley
Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta-gonad-mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB...
May 4, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/25670795/akt1-signaling-coordinates-bmp-signaling-and-%C3%AE-catenin-activity-to-regulate-second-heart-field-progenitor-development
#16
Wen Luo, Xia Zhao, Hengwei Jin, Lichan Tao, Jingai Zhu, Huijuan Wang, Brian A Hemmings, Zhongzhou Yang
Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract...
February 15, 2015: Development
https://www.readbyqxmd.com/read/25591310/-study-on-gene-transfection-in-bone-marrow-mesenchymal-stem-cells-mediated-by-plasmid-of-bone-morphogenetic-protein-2-loaded-lipopolysaccharide-amine-nanopolymersomes
#17
Yun Guan, Qinmei Wang, Ying Cheng, Wei Teng, Hongzhang Huang
OBJECTIVE: To evaluate the combination of lipopolysaccharide-amine nanopolymersomes (LNPs), as a gene vector, with target gene and the transfection in bone marrow mesenchymal stem cells (BMSCs) so as to provide a preliminary experiment basis for combination treatment of bone defect with gene therapy mediated by LNPs and stem cells. METHODS: Plasmid of bone morphogenetic protein 2 (pBMP-2)-loaded LNPs (pLNPs) were prepared. The binding ability of pLNPs to pBMP-2 was evaluated by a gel retardation experiment with different ratios of nitrogen to phosphorus elements (N/P)...
October 2014: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/25558247/modeling-murine-yolk-sac-hematopoiesis-with-embryonic-stem-cell-culture-systems
#18
Brandoch D Cook
The onset of hematopoiesis in mammals is defined by generation of primitive erythrocytes and macrophage progenitors in embryonic yolk sac. Laboratories have met the challenge of transient and swiftly changing specification events from ventral mesoderm through multipotent progenitors and maturing lineage-restricted hematopoietic subtypes, by developing powerful in vitro experimental models to interrogate hematopoietic ontogeny. Most importantly, studies of differentiating embryonic stem cell derivatives in embryoid body and stromal coculture systems have identified crucial roles for transcription factor networks (e...
October 2014: Frontiers in Biology
https://www.readbyqxmd.com/read/25544748/a-role-for-bmp-induced-homeobox-gene-mixl1-in-acute-myelogenous-leukemia-and-identification-of-type-i-bmp-receptor-as-a-potential-target-for-therapy
#19
Aaron Raymond, Bin Liu, Hong Liang, Caimiao Wei, Michele Guindani, Yue Lu, Shoudan Liang, Lisa S St John, Jeff Molldrem, Lalitha Nagarajan
Mesoderm Inducer in Xenopus Like1 (MIXL1), a paired-type homeobox transcription factor induced by TGF-β family of ligands is required for early embryonic specification of mesoderm and endoderm. Retrovirally transduced Mixl1 is reported to induce acute myelogenous leukemia (AML) with a high penetrance. But the mechanistic underpinnings of MIXL1 mediated leukemogenesis are unknown. Here, we establish the protooncogene c-REL to be a transcriptional target of MIXL1 by genome wide chromatin immune precipitation...
December 30, 2014: Oncotarget
https://www.readbyqxmd.com/read/25521758/mixl1-and-flk1-are-key-players-of-wnt-tgf-%C3%AE-signaling-during-dmso-induced-mesodermal-specification-in-p19-cells
#20
Seung-Cheol Choi, Ji-Hyun Choi, Long-Hui Cui, Ha-Rim Seo, Jong-Ho Kim, Chi-Yeon Park, Hyung-Joon Joo, Jae-Hyoung Park, Soon-Jun Hong, Cheol-Woong Yu, Do-Sun Lim
Dimethyl sulfoxide (DMSO) is widely used to induce multilineage differentiation of embryonic and adult progenitor cells. To date, little is known about the mechanisms underlying DMSO-induced mesodermal specification. In this study, we investigated the signaling pathways and lineage-determining genes involved in DMSO-induced mesodermal specification in P19 cells. Wnt/β-catenin and TGF-β superfamily signaling pathways such as BMP, TGF-β and GDF1 signaling were significantly activated during DMSO-induced mesodermal specification...
August 2015: Journal of Cellular Physiology
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