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Stem Cell Niche

Eusebio Perdiguero, Victoria Moiseeva, Pura Muñoz-Cánoves
The maintenance of adult stem cells in their normal quiescent state depends on intrinsic factors and extrinsic signals originating from their microenvironment (also known as the stem cell niche). In skeletal muscle, its stem cells (satellite cells) lose their regenerative potential with aging, and this has been attributed, at least in part, to both age-associated changes in the satellite cells as in the niche cells, which include resident fibro-adipogenic progenitors (FAPs), macrophages, and endothelial cells, among others...
February 16, 2019: Methods in Molecular Biology
Peter P Nimiritsky, Roman Yu Eremichev, Natalya A Alexandrushkina, Anastasia Yu Efimenko, Vsevolod A Tkachuk, Pavel I Makarevich
Regeneration is a fundamental process attributed to the functions of adult stem cells. In the last decades, delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading means of cell therapy. However, adult stem cells cannot complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding the mechanisms underlying mammalian regeneration leads us to an assumption that improved outcomes of cell therapy require a specific microenvironment that is generated in damaged areas prior to stem cell delivery...
February 14, 2019: International Journal of Molecular Sciences
Eva Kammergruber, Carolin Rahn, Barbara Nell, Simone Gabner, Monika Egerbacher
OBJECTIVE: The morphology of the corneal epithelium in two age groups of horses is described. Distribution patterns of proliferation-, differentiation-, stem cell-associated markers and cell junction proteins were assessed. METHODS: Corneal samples from 12 horses (six foals and six adult horses) were analyzed after H&E staining and immunohistochemistry using the following antibodies: E-cadherin, β-catenin, Connexin 43 (Cx43), tight junction protein 1 (TJP1), cytokeratin (CK) 14, CK 19, CK 3, CK 10, vimentin, Ki67, p63, nerve growth factor (NGF), ABCG2, and epithelial growth factor receptor...
February 14, 2019: Veterinary Ophthalmology
Takahiko Imai, Hiroki Tanaka, Yoko Hamazaki, Nagahiro Minato
Adult long-term hematopoiesis depends on sustaining hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM) niches, where their balance of quiescence, self-renewal, and hematopoietic differentiation is tightly regulated. While various BM stroma cells that produce niche factors have been identified, regulation of the intrinsic responsiveness of HSPCs to the niche factors remains elusive. We previously reported that mice deficient for Sipa1, a Rap1 GTPase-activating protein, develop diverse hematopoietic disorders of late onset...
February 15, 2019: Cancer Science
Kenneth Kaushansky, Huichun Zhan
The hematopoietic niche is composed of endothelial cells, mesenchymal stromal cells of several types, and megakaryocytes, and functions to support the survival, proliferation, and differentiation of normal hematopoietic stem cells (HSCs). An abundance of evidence from a range of hematological malignancies supports the concept that the niche also participates in the pathogenesis of malignant hematopoiesis, differentially supporting malignant stem or progenitor cells over that of normal blood cell development...
February 14, 2019: Annals of the New York Academy of Sciences
Georges J M Maestroni
Hematopoiesis produce every day billions of blood cells and takes place in the bone marrow (BM) by the proliferation and differentiation of hematopoietic stem cells (HSC). HSC are found mainly adjacent to the BM vascular sinusoids where endothelial cells and mesenchimal stromal cells promote HSC maintenance by producing a variety of factors. Other cell types that regulate HSC niches include sympathetic nerves, non-myelinating Schwann cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes...
February 14, 2019: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Melissa Dipp-Álvarez, Alfredo Cruz-Ramírez
Comparative genomics has revealed that members of early divergent lineages of land plants share a set of highly conserved transcription factors (TFs) with flowering plants. While gene copy numbers have expanded through time, it has been predicted that diversification, co-option, and reassembly of gene regulatory networks implicated in development are directly related to morphological innovations that led to more complex land plant bodies. Examples of key networks have been deeply studied in Arabidopsis thaliana , such as those involving the AINTEGUMENTA (ANT) gene family that encodes AP2-type TFs...
2019: Frontiers in Plant Science
Ting Li, An Yan, Neha Bhatia, Alphan Altinok, Eldad Afik, Pauline Durand-Smet, Paul T Tarr, Julian I Schroeder, Marcus G Heisler, Elliot M Meyerowitz
In plants mechanical signals pattern morphogenesis through the polar transport of the hormone auxin and through regulation of interphase microtubule (MT) orientation. To date, the mechanisms by which such signals induce changes in cell polarity remain unknown. Through a combination of time-lapse imaging, and chemical and mechanical perturbations, we show that mechanical stimulation of the SAM causes transient changes in cytoplasmic calcium ion concentration (Ca2+ ) and that transient Ca2+ response is required for downstream changes in PIN-FORMED 1 (PIN1) polarity...
February 13, 2019: Nature Communications
Tania Incitti, Alessandro Magli, Radbod Darabi, Ce Yuan, Karena Lin, Robert W Arpke, Karim Azzag, Ami Yamamoto, Ron Stewart, James A Thomson, Michael Kyba, Rita C R Perlingeiro
Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSCs) allows the generation of myogenic progenitors endowed with enhanced regenerative capacity. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages...
February 13, 2019: Proceedings of the National Academy of Sciences of the United States of America
Irit Meivar-Levy, Fatima Zoabi, Gil Nardini, Eugenia Manevitz-Mendelson, Gil S Leichner, Oranit Zadok, Michael Gurevich, Eytan Mor, Simona Dima, Irinel Popescu, Aviv Barzilai, Sarah Ferber, Shoshana Greenberger
BACKGROUND: Insulin-dependent diabetes is a multifactorial disorder that could be theoretically cured by functional pancreatic islets and insulin-producing cell (IPC) implantation. Regenerative medicine approaches include the potential for growing tissues and organs in the laboratory and transplanting them when the body cannot heal itself. However, several obstacles remain to be overcome in order to bring regenerative medicine approach for diabetes closer to its clinical implementation; the cells generated in vitro are typically of heterogenic and immature nature and the site of implantation should be readily vascularized for the implanted cells to survive in vivo...
February 13, 2019: Stem Cell Research & Therapy
Akshitkumar M Mistry, David J Wooten, L Taylor Davis, Bret C Mobley, Vito Quaranta, Rebecca A Ihrie
Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases...
February 12, 2019: Scientific Reports
Li Chen, Kaikai Shi, Thomas Levin Andersen, Weimin Qiu, Moustapha Kassem
Factors mediating mobilization of osteoblastic stem and progenitor cells from their bone marrow niche to be recruited to bone formation sites during bone remodeling are poorly known. We have studied secreted factors present in the bone marrow microenvironment and identified KIAA1199 (also known as CEMIP, cell migration inducing hyaluronan binding protein) in human bone biopsies as highly expressed in osteoprogenitor reversal cells (Rv.C) recruited to the eroded surfaces (ES), which are the future bone formation sites...
February 12, 2019: Cell Death & Disease
Sandra Pinho, Paul S Frenette
The haematopoietic stem cell (HSC) microenvironment in the bone marrow, termed the niche, ensures haematopoietic homeostasis by controlling the proliferation, self-renewal, differentiation and migration of HSCs and progenitor cells at steady state and in response to emergencies and injury. Improved methods for HSC isolation, driven by advances in single-cell and molecular technologies, have led to a better understanding of their behaviour, heterogeneity and lineage fate and of the niche cells and signals that regulate their function...
February 11, 2019: Nature Reviews. Molecular Cell Biology
Yuan Gao, Ying Mao, Rong-Gang Xu, Ruibao Zhu, Ming Zhang, Jin Sun, Da Shen, Ping Peng, Ting Xie, Jian-Quan Ni
In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study, we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation...
January 30, 2019: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Yazmin Brown, Susan Hua, Pradeep S Tanwar
The identity of cancer stem cells (CSCs) remains an enigma, with the question outstanding of whether CSCs are fixed entities or plastic cell states in response to microenvironmental cues. Recent evidence highlights the power of the tumor microenvironment to dictate CSC functionality and spatiotemporal regulation that gives rise to tumor heterogeneity. This microenvironmental regulation of CSCs parallels that of normal tissues, whereby resident stem cells reside within specialized microenvironments or 'niches', which provide the cellular and molecular signals that wire every aspect of stem cell behavior and fate...
February 8, 2019: International Journal of Biochemistry & Cell Biology
A R Pereira, D Trivanović, M Herrmann
Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications...
February 11, 2019: European Cells & Materials
Giovanna Lacava, Fulvio Laus, Andrea Amaroli, Andrea Marchegiani, Roberta Censi, Piera Di Martino, Toru Yanagawa, Maria Giovanna Sabbieti, Dimitrios Agas
With advancing age have been observed bone and bone marrow phenotypic alterations due to the impaired bone tissue homeostatic features, involving bone remodeling, and bone marrow niche ontogeny. The complex "inflamm-aging" pathological scenario that culminates with osteopenia and mesenchymal/stromal and hematopoietic stem cell commitment breakdown, is controlled by cellular and molecular intramural components comprising adapter proteins such as the sequestosome 1 (p62/SQSTM1). p62, a "multiway function" protein, has been reported as an effective anti-inflammatory, bone-building factor...
February 10, 2019: Journal of Cellular Physiology
Hironobu Nishina, Chisa Katou-Ichikawa, Mizuki Kuramochi, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma (MFH)-derived cloned cells, recognizes somatic stem cells (bone-marrow/hair follicle stem cells). We investigated the distribution of cells immunoreactive to A3 in the developing rat intestine (particularly, the colon), focusing on the ontogenic kinetics of A3-positive cells. In the rat intestine, A3 labeled spindle-shaped stromal cells localized in the submucosa and labeled endothelial cells of capillaries in the lamina propria forming villi in the early development stage...
January 2019: Journal of Toxicologic Pathology
Amjd Ibraheem, Oshrat Attar-Schneider, Mahmoud Dabbah, Osnat Dolberg Jarchowsky, Shelly Tartakover Matalon, Michael Lishner, Liat Drucker
Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interaction with the microenvironment promotes disease progression and drug resistance. Previously, we have shown that MM cells cocultured with BM-mesenchymal stem cells (MSCs) comodulated cells' phenotype in a MAPKs/translation initiation (TI)-dependent manner. Dissection of the coculture model showed that BM-MSCs secretomes and microvesicles (MVs) participate in this crosstalk. Here, we addressed the role of the BM-MSCs extracellular matrix (ECM)...
January 23, 2019: Translational Research: the Journal of Laboratory and Clinical Medicine
Pinyang Cheng, Erika A Eksioglu, Xianghong Chen, Wendy Kandell, Thu Le Trinh, Ling Cen, Jin Qi, David A Sallman, Yu Zhang, Nhan Tu, William A Adams, Chunze Zhang, Jinhong Liu, John L Cleveland, Alan F List, Sheng Wei
Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized. Here we report an increased expression of PD-1 on HSPCs and PD-L1 on MDSCs in MDS versus healthy donors, and that this checkpoint is also activated in S100A9 transgenic (S100A9Tg) mice, and by treatment of BM mononuclear cells (BM-MNC) with S100A9...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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