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1.
This article reports events connected to cell survival and Botrytis cinerea infection development in cell suspension cultures of two tomato cultivars which show different levels of susceptibility to the pathogen: cv. Corindo (more susceptible) and cv. Perkoz (less susceptible). In parallel changes in reactive oxygen (ROS) and nitrogen (RNS) species generation and in S-nitrosoglutathione reductase (GSNOR) activity were studied. In vivo staining methods with acridine orange (AO) and ethidium bromide (EB) as well as fluorescent microscopy were used to assess tomato and B. cinerea cells death. The biochemical studies of ROS and RNS concentrations in plant cell extract were complemented by in vivo ROS and nitric oxide (NO) imaging using nitro blue tetrazolium (NBT), diaminobenzidine (DAB) and diaminofluorescein diacetate (DAF-DA) staining methods, and confocal microscope technique. B. cinerea infection proceeded slower in Perkoz cell cultures. It was evidenced by measuring the pathogen conidia germination and germination tube development in which nuclei revealing cell death dominated. Two different types of tomato cell death were observed: cells with necrotic nuclei dominated in Corindo whereas in Perkoz cells with characteristic of vacuolar death type prevailed. In Perkoz cells, constitutive levels of NO and S-nitrosothiols (SNO) were significantly higher and hydrogen peroxide (H2O2) and superoxide anion (O2 ?) concentrations were slightly higher as compared with Corindo cells. Moreover, increases in these molecule concentrations as a result of B. cinerea inoculation were observed in both, Perkoz and Corindo cell cultures. The enzymatic GSNOR activity seems to be an important player in controlling the SNO level in tomato cells. Involvements of the studied compounds in molecular mechanisms of tomato resistance to B. cinerea are discussed in the paper. 相似文献
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Stanislava Stanojević Nataša Kuštrimović Katarina Mitić Vesna Vujić Iva Aleksić Mirjana Dimitrijević 《Life sciences》2013
Aims
Macrophages are heterogeneous population of inflammatory cells and, in response to the microenvironment, become differentially activated. The objective of the study was to explore macrophage effector functions during different inflammatory conditions in two rat strains.Main methods
We have investigated the effects of in vivo treatment with mast cell-degranulating compound 48/80 and/or thioglycollate on peritoneal macrophage phagocytosis and capacity to secrete hydrogen peroxide (H2O2), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in Dark Agouti (DA) and Albino Oxford (AO) rat strains. Besides, fresh peritoneal cells were examined for the expression of ED1, ED2 and CD86 molecules.Key findings
In thioglycollate-elicited macrophages, increased proportion of ED1 + cells was accompanied with elevated phagocytosis of zymosan (DA strain), whereas increased expression level of CD86 molecule on ED2 + macrophages matched elevated secretory capacity for H2O2, TNF-α and NO (AO rats). Although mast cell degranulation induced by compound 48/80 increased the percentages of ED2 + macrophages in both rat strains, the proportion of ED2 + cells expressing CD86 molecule was decreased and increased in DA and AO rats, respectively. Furthermore, in DA strain compound 48/80 diminished macrophage secretion of NO, but stimulated all macrophage functions tested in AO strain. If applied concomitantly, the compound 48/80 additively increased macrophage activity induced by thioglycollate in AO rats.Significance
Macrophages from DA and AO rat strains show different susceptibility to mediators released from mast cells, suggesting that strain-dependant predisposition(s) toward particular activation pattern is decisive for the macrophage efficacy in response to inflammatory agents. 相似文献4.
Vanessa E. Jahnke Odile Sabido Aurélia Defour Josiane Castells Etienne Lefai Damien Roussel Damien Freyssenet 《PloS one》2010,5(1)
Background
Mitochondria can sense signals linked to variations in energy demand to regulate nuclear gene expression. This retrograde signaling pathway is presumed to be involved in the regulation of myoblast proliferation and differentiation. Rhabdomyosarcoma cells are characterized by their failure to both irreversibly exit the cell cycle and complete myogenic differentiation. However, it is currently unknown whether mitochondria are involved in the failure of rhabdomyosarcoma cells to differentiate.Methodology/Principal Findings
Mitochondrial biogenesis and metabolism were studied in rat L6E9 myoblasts and R1H rhabdomyosacoma cells during the cell cycle and after 36 hours of differentiation. Using a combination of flow cytometry, polarographic and molecular analyses, we evidenced a marked decrease in the cardiolipin content of R1H cells cultured in growth and differentiation media, together with a significant increase in the content of mitochondrial biogenesis factors and mitochondrial respiratory chain proteins. Altogether, these data indicate that the mitochondrial inner membrane composition and the overall process of mitochondrial biogenesis are markedly altered in R1H cells. Importantly, the dysregulation of protein-to-cardiolipin ratio was associated with major deficiencies in both basal and maximal mitochondrial respiration rates. This deficiency in mitochondrial respiration probably contributes to the inability of R1H cells to decrease mitochondrial H2O2 level at the onset of differentiation.Conclusion/Significance
A defect in the regulation of mitochondrial biogenesis and mitochondrial metabolism may thus be an epigenetic mechanism that may contribute to the tumoral behavior of R1H cells. Our data underline the importance of mitochondria in the regulation of myogenic differentiation. 相似文献5.
A V Guitart C Debeissat F Hermitte A Villacreces Z Ivanovic H Boeuf V Praloran 《Cell death and differentiation》2011,18(1):174-182
Oxygen (O2) concentrations in bone marrow vary from 4% in capillaries to <0.1% in subendosteum, in which hematopoietic stem cells reside in specific niches. Culture at low O2 concentrations (3, 1 and 0.1%) influences hematopoietic stem and progenitor cells survival, proliferation and differentiation, depending on their level of differentiation. Culture of human CD34+ cells at low O2 concentrations (O2 ⩽3%) maintains stem cell engraftment potential better than at 20% O2 (NOD/Scid xenograft model). In contrast, progenitors disappear from cultures at/or <1% O2 concentrations. A very low O2 concentration (0.1%) induces CD34+ quiescence in G0. The exploration of molecules and mechanisms involved in hematopoietic stem and progenitor cells'' quiescence and differentiation related to low O2 concentrations is unfeasible with primary CD34+ cells. Therefore, we performed it using murine hematopoietic nonleukemic factor-dependent cell Paterson (FDCP)-Mix progenitor cell line. The culture of the FDCP-Mix line at 0.1% O2 induced in parallel G0 quiescence and granulo-monocytic differentiation of most cells, whereas a minority of undifferentiated self-renewing cells remained in active cell cycle. Hypoxia also induced hypophosphorylation of pRb and increased the expression of p27KIP1, the two proteins that have a major role in the control of G0 and G1 to S-phase transition. 相似文献
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Karina Ckless Samantha R. Hodgkins Jennifer L. Ather Rebecca Martin Matthew E. Poynter 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
While many of the contributing cell types and mediators of allergic asthma are known, less well understood are the factors that induce allergy in the first place. Amongst the mediators speculated to affect initial allergen sensitization and the development of pathogenic allergic responses to innocuous inhaled antigens and allergens are exogenously or endogenously generated reactive oxygen species (ROS) and reactive nitrogen species (RNS).Scope of review
The interactions between ROS/RNS, dendritic cells (DCs), and CD4+ T cells, as well as their modulation by lung epithelium, are of critical importance for the genesis of allergies that later manifest in allergic asthma. Therefore, this review will primarily focus on the initiation of pulmonary allergies and the role that ROS/RNS may play in the steps therein, using examples from our own work on the roles of NO2 exposure and airway epithelial NF-κB activation.Major conclusions
Endogenously generated ROS/RNS and those encountered from environmental sources interact with epithelium, DCs, and CD4+ T cells to orchestrate allergic sensitization through modulation of the activities of each of these cell types, which quantitiatively and qualitatively dictate the degree and type of the allergic asthma phenotype.General significance
Knowledge of the effects of ROS/RNS at the molecular and cellular levels has the potential to provide powerful insight into the balance between inhalational tolerance (the typical immunologic response to an innocuous inhaled antigen) and allergy, as well as to potentially provide mechanistic targets for the prevention and treatment of asthma. 相似文献7.
Bone marrow (BM)-derived stem and progenitor cell functions including self-renewal, differentiation, survival, migration, proliferation, and mobilization are regulated by unique cell-intrinsic and -extrinsic signals provided by their microenvironment, also termed the “niche.” Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), play important roles in regulating stem and progenitor cell functions in various physiologic and pathologic responses. The low level of H2O2 in quiescent hematopoietic stem cells (HSCs) contributes to maintaining their “stemness,” whereas a higher level of H2O2 within HSCs or their niche promotes differentiation, proliferation, migration, and survival of HSCs or stem/progenitor cells. Major sources of ROS are NADPH oxidase and mitochondria. In response to ischemic injury, ROS derived from NADPH oxidase are increased in the BM microenvironment, which is required for hypoxia and hypoxia-inducible factor-1α expression and expansion throughout the BM. This, in turn, promotes progenitor cell expansion and mobilization from BM, leading to reparative neovascularization and tissue repair. In pathophysiological states such as aging, atherosclerosis, heart failure, hypertension, and diabetes, excess amounts of ROS create an inflammatory and oxidative microenvironment, which induces cell damage and apoptosis of stem and progenitor cells. Understanding the molecular mechanisms of how ROS regulate the functions of stem and progenitor cells and their niche in physiological and pathological conditions will lead to the development of novel therapeutic strategies. 相似文献
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Alexander V. Zhdanov Ruslan I. Dmitriev Anna V. Golubeva Svetlana A. Gavrilova Dmitri B. Papkovsky 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Along with other regulators of cell metabolism, hypoxia-inducible factors HIF-1 and HIF-2 differentially regulate cell adaptation to hypoxia. Switches in HIF-1/HIF-2 signaling in chronic hypoxia have not been fully investigated.Methods
Proliferation, viability, apoptosis, neuronal and bioenergetic markers, mitochondrial function, respiration, glycolysis, HIF signalling, responses to O2 and glucose deprivation (OGD) were examined using tumor PC12 and SH-SY5Y cells continuously grown at 3% O2.Results
Hypoxic PC12 cells (H-cells) exhibit reduced proliferation and histone H4 acetylation, NGF-independent differentiation, activation of AMPK, inhibition of Akt, altered mitochondria and response to NGF. Cellular cytochrome c is increased with no effect on apoptosis. Reduction in respiration has minor effect on cellular ATP which is maintained through activated uptake (GLUT1) and utilization (HK2, PFK2) of glucose. H-cells exhibit resistance to OGD linked to increased glycogen stores. HIF-2alpha protein is decreased without changes in mRNA. Unlike HIF-1alpha, HIF-2alpha is not stabilized pharmacologically or by O2 deprivation. Capacity for HIF-2alpha stabilization is partly restored when H-cells are cultured at normoxia. In low-respiring SH-SY5Y cells cultured under the same conditions HIF-2alpha stabilization and energy budget are not affected.Conclusions
In chronically hypoxic PC12 cells glycolytic energy budget, increased energy preservation and low susceptibility to OGD are observed. HIF-2alpha no longer orchestrates adaptive responses to anoxia.General significance
Demonstrated switch in HIF-1/HIF-2 signaling upon chronic hypoxia can facilitate cell survival in energy crisis, by regulating balance between energy saving and decrease in proliferation, on one hand and active cell growth and tumor expansion, on the other. 相似文献10.
Seahyoung Lee Ina Yun Onju Ham Se-Yeon Lee Chang Yeon Lee Jun-Hee Park Jiyun Lee Hyang-Hee Seo Eunhyun Choi Ki-Chul Hwang 《Biological research》2015,48(1)
Background
Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated.Results
H2O2 (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2.Conclusions
These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues. 相似文献11.
Fang Tan Samit Ghosh Flaubert Mbeunkui Robert Thomas Joshua A Weiner Solomon F Ofori-Acquah 《BMC molecular biology》2010,11(1):91
Background
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined. 相似文献12.
Ya-Dan Wen Hong Wang Sok-Hong Kho Suguro Rinkiko Xiong Sheng Han-Ming Shen Yi-Zhun Zhu 《PloS one》2013,8(2)
Background
Hydrogen sulfide (H2S) has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer''s disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H2S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H2O2) induced endothelial cells damage.Methodology and Principal Findings
H2S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs) exposed to H2O2. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H2S. In contrast, in H2O2 exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H2S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H2O2 exposed cells. ROS and lipid peroxidation, as assessed by measuring H2DCFDA, dihydroethidium (DHE), diphenyl-l-pyrenylphosphine (DPPP) and malonaldehyde (MDA) levels, were also inhibited by H2S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG), a selective inhibitor of cystathionine γ-lyase (CSE), abolished the protective effects of H2S donors.Innovation
This study is the first to show that H2S can inhibit H2O2 mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences.Significance
H2S may protect against atherosclerosis by preventing H2O2 induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress. 相似文献13.
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F. J. Bergersen 《Protoplasma》1994,183(1-4):49-61
Summary A simulation model is presented for the distribution and consumption of O2 in infected cells of soybean root nodule central tissue. It differs from earlier models in closer adherence to observed structure and embodies new morphometric data about the distribution of > 12,000 mitochondria per cell and about the geometry of the gas-filled intercellular spaces near which the mitochondria are located. The model cell is a rhombic dodecahedron and O2 enters only through interfaces (totalling 26% of the cell surface) with 24 gas-filled intercellular spaces. These spaces are located at the edges of each rhombic face of the cell, forming an interconnected network over the cell suface. Next, O2 is distributed through the cytoplasm by a leghaemoglobin-facilitated diffusive process, initially between the mitochondria and amyloplasts in the outer layers of the cell and then between > 6,000 symbiosomes (each containing 6 bacteroids) towards the central nucleus. The symbiosomes and mitochondria consume O2, but impede its diffusion; all O2 entering symbiosomes is considered to be consumed there. For the calculations, the cell is considered to consist of 24 structural units, each beneath one of the intercellular spaces, and each is divided into 126 layers, 0.2 m thick, in and through which O2 is consumed and diffused. Rates of consumption of O2 and of N2 fixation in each diffusion layer were calculated from previously-established kinetics of respiration by mitochondria and bacteroids isolated from soybean nodules and from established relationships between bacteroid respiration and N2 fixation. The effects of varying the O2-supply concentration and the concentration and type of energy-yielding substrates were included in the simulations. When the model cell was supplied with 0.5 mM malate, mitochondria accounted for a minimum of 50% of the respiration of the model cell and this percentage increased with increased concentration of the O2 supply. Gradients of concentrations of free O2 dissolved in the cytoplasm were steepest near the cell surface and in this location respiration by mitochondria appeared to exert a marked protective effect for nitrogen fixation in layers deeper within the cell. Estimates of N2 fixation per nodule, calculated from the model cell, were similar to those calculated from field measurements.Abbreviations Lb
leghaemoglobin
- LbO2
oxyleghaemoglobin
- [O2]
concentration of free, dissolved O2
- e.m.
electron micrograph
Dedicated to the memory of Professor John G. Torrey 相似文献
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Shuxian Jiang Byeong-Chel Lee Yigong Fu Shalom Avraham Bing Lim Hava Karsenty Avraham 《PloS one》2010,5(3)
Background
Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.Methodology/Principal Findings
To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES) cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs) under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Conclusions/Significance
Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate. 相似文献16.
Tomoyuki Watanabe Masao Saotome Mamoru Nobuhara Atsushi Sakamoto Tsuyoshi Urushida Hideki Katoh Hiroshi Satoh Makoto Funaki Hideharu Hayashi 《Experimental cell research》2014
Purpose
Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance.Methods and Results
DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨm) depolarization, exhibited attenuated insulin signaling and 2-deoxy-d-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H2O2), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨm depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H2O2-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨm depolarization and impaired 2-DG uptake, however they improved insulin signaling.Conclusions
A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. 相似文献17.
Luciana Dini Majdi Dwikat Elisa Panzarini Cristian Vergallo Bernadetta Tenuzzo 《Bioelectromagnetics》2009,30(5):352-364
This study deals with the morphofunctional influence of 72 h exposure to a 6 mT static magnetic field (SMF) during differentiation induced by 50 ng/ml 12‐O‐tetradecanoyl‐13‐phorbol acetate (TPA) in human leukaemia U937 cells. The cell morphology of U937 cells was investigated by optic and electron microscopy. Specific antibodies and/or molecules were used to label CD11c, CD14, phosphatidylserine, F‐actin and to investigate the distribution and activity of lysosomes, mitochondria and SER. [Ca2+]i was evaluated with a spectrophotometer. The degree of differentiation in SMF‐exposed cells was lower than that of non‐exposed cells, the difference being exposure time‐dependent. SMF‐exposed cells showed cell shape and F‐actin modification, inhibition of cell attachment, appearance of membrane roughness and large blebs and impaired expression of specific macrophagic markers on the cell surface. The intracellular localization of SER and lysosomes was only partially affected by exposure. A significant localization of mitochondria with an intact membrane potential at the cell periphery in non‐exposed, TPA‐stimulated cells was observed; conversely, in the presence of SMF, mitochondria were mainly localised near the nucleus. In no case did SMF exposure affect cell viability. The sharp intracellular increase of [Ca2+]i could be one of the causes of the above‐described changes. Bioelectromagnetics 30:352–364, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
18.
Mesophyll cells isolated from Zinnia elegans L. cv. Canary Bird were cultured for 96 h in a liquid medium containing 0.1 mg l-1 -naphthaleneacetic acid and 1 mg l-1 benzyladenine in which both differentiation of tracheary elements (TE) and cell division were induced, or in a medium containing 0.1 mg l-1 -naphthaleneacetic acid and 0.001 mg l-1 benzyladenine, in which cell division was induced but TE differentiation was not. Lignification was found to occur only in the former medium, fairly synchronously after 76 h of culture, 5 h later than the onset of visible secondary wall thickening. Changes in the soluble phenolics were not correlated with TE differentiation. Of three important enzymes which have been reported to play a role in TE differentiation, the activity of phenylalanine ammonia-lyase (EC 4.3.1.5) in the TE-inductive culture was higher than that in the control culture between 72 and 96 h of culture, when TE differentiation progressed and lignin was synthesized actively. O-Methyltransferase (EC 2.1.1.6) activity was higher in the control culture than in the TE-inductive culture, indicating that this enzyme was not a marker enzyme of TE differentiation. The activities of peroxidases (EC 1.11.1.7), one extractable and the other nonextractable, with CaCl2 from the cell walls, reached peaks at 72 h (just before lignification) and 84 h of culture (active lignin synthesis), respectively, in the TE-inductive culture only, whereas the activity of soluble peroxidase showed a similar pattern of increase in the TE-inductive to the control culture. These results indicate that phenylalanine ammonia-lyase and peroxidase bound to the cell walls can be marker proteins for the differentiation of TE.Abbreviations OMT
O-methyltransferase
- PO
peroxidase
- PAL
phenylalanine ammonia-lyase
- TE
tracheary element(s) 相似文献
19.
Hye-Ryun?Kim Jong-Hee?Lee Hye-Ryeon?Heo Se-Ran?Yang Kwon-Soo?Ha Won?Sun?Park Eun-Taek?Han Haengseok?Song
Background
Aside from its importance in reproduction, estrogen (E2) is known to regulate the proliferation and differentiation of hematopoietic stem cells in rodents. However, the regulatory role of E2 in human hematopoietic system has not been investigated. The purpose of this study is to investigate the effect of E2 on hematopoietic differentiation using human pluripotent stem cells (hPSCs).Results
E2 improved hematopoietic differentiation of hPSCs via estrogen receptor alpha (ER-α)-dependent pathway. During hematopoietic differentiation of hPSCs, ER-α is persistently maintained and hematopoietic phenotypes (CD34 and CD45) were exclusively detected in ER-α positive cells. Interestingly, continuous E2 signaling is required to promote hematopoietic output from hPSCs. Supplementation of E2 or an ER-α selective agonist significantly increased the number of hemangioblasts and hematopoietic progenitors, and subsequent erythropoiesis, whereas ER-β selective agonist did not. Furthermore, ICI 182,780 (ER antagonist) completely abrogated the E2-induced hematopoietic augmentation. Not only from hPSCs but also from human umbilical cord bloods, does E2 signaling potentiate hematopoietic development, suggesting universal function of E2 on hematopoiesis.Conclusions
Our study identifies E2 as positive regulator of human hematopoiesis and suggests that endocrine factors such as E2 influence the behavior of hematopoietic stem cells in various physiological conditions.20.