103. ROLE OF CANDIDATE STEM/PROGENITOR CELLS IN A MOUSE MODEL OF ENDOMETRIAL MENSTRUAL BREAKDOWN AND REPAIR

2009 ◽  
Vol 21 (9) ◽  
pp. 22
Author(s):  
T. J. Kaitu'u-Lino ◽  
L. Ye ◽  
C. E. Gargett
Keyword(s):  
Confocal Microscopy ◽  
Mouse Model ◽  
Progenitor Cells ◽  
Functional Role ◽  
Double Immunofluorescence ◽  
Regenerative Capacity ◽  
Brdu Label ◽  
Nuclear Label ◽  
Human And Mouse

Adult stem/progenitor cells (SPC) identified in human and mouse endometrium may be responsible for its remarkable regenerative capacity (1), however a functional role for SPC in menstruation is yet to be established. This study aimed to identify label retaining cells (LRC) as candidate epithelial SPC involved in the rapid re-epithelisation of the uterine surface in a mouse model; tissue SPCs are quiescent and will retain label (BrdU), while label is diluted out as transit amplifying cells proliferate. Mice were ovariectomised and endometrial breakdown and repair induced, mimicking menstruation in women (2). BrdU (50µg/g) was administered intraperitoneally 8.5 days before endometrial repair. Tissue was collected to assess initial labelling, and following four chase periods prior to and during endometrial repair (n=3-5 animals/group) and immunostained for BrdU. LRC were categorised as minimal (<50% nuclear label), partial (50-75%) and full (100%) and counted in the luminal (LE) and glandular (GE) epithelial compartments for each group. The majority of LE (91.4±1.9%; mean±SEM) and 35±3.8% of GE were initially labelled. During breakdown and repair the percentage of full LE LRC (38±13.1% vs 1.3±1.1%) and partial LE LRC (49.1±4.3% vs 1.8±0.7%) significantly decreased (p≤0.01) whilst minimal LRC significantly increased (12.9±3.5% vs 85.2±4.3%; p≤0.001) indicating dilution of BrdU label as cells proliferated. In contrast full, partial and minimal GE LRC did not significantly change throughout endometrial breakdown and repair. The rapid dilution of BrdU label in the LE suggests that the transit amplifying population are responsible for the rapid proliferation observed, whilst the lack of change of BrdU in the GE suggests that GE may be a source of SPC. Double immunofluorescence and confocal microscopy are currently underway to further characterise the LRC population in this model. This study provides some of the first insights into the contribution of candidate SPC to endometrial repair.

scholarly journals Reepithelialization of the Uterine Surface Arises from Endometrial Glands: Evidence from a Functional Mouse Model of Breakdown and Repair

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3386-3395 ◽  
Author(s):  
Tu'uhevaha J. Kaitu'u-Lino ◽  
Louie Ye ◽  
Caroline E. Gargett
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Functional Role ◽  
Estrogen Receptor Α ◽  
Glandular Epithelium ◽  
Regenerative Capacity ◽  
Adult Mice ◽  
Functionally Diverse ◽  
Epithelial Progenitor Cells ◽  
Human And Mouse

The human endometrium is highly regenerative undergoing monthly cycles of growth and regression. Endometrial repair after menses is a critical component of the cycle; however, little is understood about the mechanisms behind this rapid process. Adult stem/progenitor cells identified in human and mouse endometrium may be responsible for its remarkable regenerative capacity; however, a functional role for stem/progenitor cells in menstruation is yet to be established. This study aimed to identify label retaining cells as candidate epithelial stem or progenitor cells involved in the rapid reepithelization of the uterine surface in our functional mouse model of endometrial breakdown and repair. Adult mice were pulse labeled with bromodeoxyuridine before endometrial breakdown and repair was induced. Throughout endometrial breakdown and repair, very rapid dilution of bromodeoxyuridine label was observed in the luminal epithelium, whereas label within the glandular epithelium remained constant. Importantly, glandular epithelial cells were shown to proliferate selectively in response to endometrial repair, and the majority strongly expressed estrogen receptor-α at this time. This is the first study to demonstrate a functionally diverse response during endometrial repair from the anatomically connected luminal and glandular epithelium and highlights the likelihood that the endometrial glands are the residence of epithelial progenitor cells contributing to reepithelialization of the uterine surface after menses.

Identification of antisense lncRNAs targeting GSK3β as a regulator in major depressive disorder

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1725-1738
Author(s):  
Zhifen Liu ◽  
Xinrong Li ◽  
Chen Chen ◽  
Ning Sun ◽  
Yanfang Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Progenitor Cells ◽  
Functional Role ◽  
Functional Study ◽  
Major Depressive ◽  
Before And After ◽  
Antisense Lncrnas ◽  
Novel Therapeutic

Aim: To identify lncRNAs targeting GSK3β in MDD. Materials & methods: The levels of GSK3β and its three targeting lncRNAs (gsk3β antisense AS1, AS2 and AS3) were detected in 52 patients with major depressive disorder (MDD) before and after 8 weeks of escitalopram treatment. The functional study was evaluated using the silence of lncR-gsk3βAS2/3. The correlation between lncRNA-gsk3β and 89 MDD patients was analyzed. Human neuron progenitor cells were used to investigate the functional role of lncRNA-gsk3β in MDD. Results: All three lncRNAs were downregulated in MDD patients but upregulated after treatment. Inhibition of gsk3βAS2/3 reduced GSK3β expression and its phosphorylation levels in the neuron progenitor cells. Conclusion: Our findings suggest that lncRNA-gsk3βAS3 regulates GSK3β activity in MDD and has potential as a novel therapeutic target.

scholarly journals Gremlin2 Regulates the Differentiation and Function of Cardiac Progenitor Cells via the Notch Signaling Pathway

2018 ◽  
Vol 47 (2) ◽  
pp. 579-589 ◽  
Author(s):  
Wei Li ◽  
Yaojun Lu ◽  
Ruijuan Han ◽  
Qiang Yue ◽  
Xiurong Song ◽  
...  
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Left Ventricular ◽  
Cardiac Repair ◽  
Cardiac Progenitor Cells ◽  
Cardiomyocyte Differentiation ◽  
Rt Pcr ◽  
And Function

Background/Aims: The transplantation of cardiac progenitor cells (CPCs) improves neovascularization and left ventricular function after myocardial infarction (MI). The bone morphogenetic protein antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. The present study examined the role of Grem2 in CPC differentiation and cardiac repair. Methods: To determine the role of Grem 2 during CPC differentiation, c-Kit+ CPCs were cultured in differentiation medium for different times, and Grem2, Notch1 and Jagged1 expression was determined by RT-PCR and western blotting. Short hairpin RNA was used to silence Grem2 expression, and the expression of cardiomyocyte surface markers was assessed by RT-PCR and immunofluorescence staining. In vivo experiments were performed in a mouse model of left anterior descending coronary artery ligation-induced MI. Results: CPC differentiation upregulated Grem2 expression and activated the Notch1 pathway. Grem2 knockdown inhibited cardiomyocyte differentiation, and this effect was similar to that of Notch1 pathway inhibition in vitro. Jagged1 overexpression rescued the effects of Grem2 silencing. In vivo, Grem2 silencing abolished the protective effects of CPC injection on cardiac fibrosis and function. Conclusions: Grem2 regulates CPC cardiac differentiation by modulating Notch1 signaling. Grem2 enhances the protective effect of CPCs on heart function in a mouse model of MI, suggesting its potential as the rapeutic protein for cardiac repair.

scholarly journals Functional Role of CLIC1 Ion Channel in Glioblastoma-Derived Stem/Progenitor Cells

2013 ◽  
Vol 105 (21) ◽  
pp. 1644-1655 ◽  
Author(s):  
Matteo Setti ◽  
Nicoletta Savalli ◽  
Daniela Osti ◽  
Cristina Richichi ◽  
Marina Angelini ◽  
...  
Keyword(s):  
Ion Channel ◽  
Progenitor Cells ◽  
Functional Role

Distinct Effects of SCF and Hes1 On Normal Hematopoietic Stem and Progenitor Cells During Leukemic Cell Expansion in a T-ALL Mouse Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1216-1216
Author(s):  
Chen Tian ◽  
Zhipan Cao ◽  
Qiao Li ◽  
Jinhong Wang ◽  
Zhenyu Ju ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Progenitor Cells ◽  
Real Time ◽  
Hematopoietic Cells ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Rt Pcr ◽  
Hematopoietic Stem

Abstract Abstract 1216 During leukemia development, emerging leukemic cells out-compete normal hematopoietic cells and become predominant in the body. How hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) respond to the growth of leukemic cell population is an important, yet less investigated area. Our previous study demonstrated differential effects of a leukemic environment on normal HSCs and HPCs in the Notch1-induced T-ALL mouse model (Hu X, et al. Blood 2009). We found that normal HSCs were better preserved in the leukemic bone marrow in part due to increased quiescence of the HSCs and in contrast, HPCs were exhausted during the expansion of leukemic cells. Our current work is aimed to further explore the molecular mechanisms concerning the distinct impacts of leukemic environment on normal HSCs and HPCs in the T-ALL mouse model. Given the previous report by others showing that increased secretion of stem cell factor (SCF) by myeloid leukemia cells played an important role in inducing normal HSCs/HPCs out of their niche and thus allowing leukemic cells to occupy the niche in the human-NOD/SCID xeno-graft model (Sipkins DA et al, Science 2008), we first examined the expression of SCF by ELISA, Western blot and real-time RT PCR in both normal hematopoietic and leukemic cell fractions in the Notch1-induced T-ALL mouse model as previously reported. We found that while expression of SCF in peripheral blood (PB) or bone marrow (BM) was increased in the leukemic mice, both mRNA and protein levels of SCF in normal hematopoietic cells were higher than that in leukemic cells, thereby suggesting that elevated SCF might be mainly secreted by non-leukemic cells in the leukemic hosts of our model. Further assessments on the role of SCF in leukemogenesis with the mice specifically deficient in SCF in different niche cell types are currently under investigation in our laboratory. In order to define potential mediators in HSCs in response to leukemic cell growth, a microarray study on normal HSCs isolated from T-ALL leukemic mice and the control mice was conducted. Gene expression profiling showed significantly differed expression of 169 genes (127 up and 42 down). Especially, real-time RT PCR confirmed an increase of Hes1, p21, Fbxw11, IL-18R1 and Itgb3, and a decrease of CXCR4 and Mmp2. Interestingly, the expression of Hes1 and its target gene, p21 were elevated in normal HSCs but not in HPCs, letting us to hypothesize that Hes1 might be in part mediate the different responses of HSCs and HPCs to the T-ALL leukemic environment. To test this hypothesis, we ectopically expressed Hes1 in normal hematopoietic cells and then examined their functions under the leukemic condition. BM cells from B6.SJL mice were transduced with either MSCV-Hes1-IRES-GFP or control MSCV-GFP vector. After transduction, Hes1-GFP+or control-GFP+cells were co-transplanted with the Notch1-induced T-ALL cells into lethally irradiated C57BL/6J recipients. The engrafted cells from the leukemic BM were analyzed and Hes1-GFP+or control-GFP+cells were sorted for functional assessments. Interestingly, although over-expression of Hes1 inhibited the growth of colony forming cell (CFC) in vitro, it could potentiate the long-term repopulating cells by maintaining more cells in the quiescent (G0) state in vivo. Taken together, our current study supports a role of Hes1 in mediating the distinct responses of normal HSCs and HPCs to the T-ALL leukemic environment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence

2021 ◽  
Vol 22 (9) ◽  
pp. 4796
Author(s):  
Vinoth Kumar Rethineswaran ◽  
Da Yeon Kim ◽  
Yeon-Ju Kim ◽  
WoongBi Jang ◽  
Seung Taek Ji ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Blood Circulation ◽  
Functional Role ◽  
Replicative Senescence ◽  
Endothelial Progenitor ◽  
Vascular Structures ◽  
Gsk 3Β

Endothelial progenitor cells (EPCs) are specialized cells in circulating blood, well known for their ability to form new vascular structures. Aging and various ailments such as diabetes, atherosclerosis and cardiovascular disease make EPCs vulnerable to decreasing in number, which affects their migration, proliferation and angiogenesis. Myocardial ischemia is also linked to a reduced number of EPCs and their endothelial functional role, which hinders proper blood circulation to the myocardium. The current study shows that an aminopyrimidine derivative compound (CHIR99021) induces the inhibition of GSK-3β in cultured late EPCs. GSK-3β inhibition subsequently inhibits mTOR by blocking the phosphorylation of TSC2 and lysosomal localization of mTOR. Furthermore, suppression of GSK-3β activity considerably increased lysosomal activation and autophagy. The activation of lysosomes and autophagy by GSK-3β inhibition not only prevented replicative senescence of the late EPCs but also directed their migration, proliferation and angiogenesis. To conclude, our results demonstrate that lysosome activation and autophagy play a crucial role in blocking the replicative senescence of EPCs and in increasing their endothelial function. Thus, the findings provide an insight towards the treatment of ischemia-associated cardiovascular diseases based on the role of late EPCs.

scholarly journals Effects of Brain-Derived Neurotrophic Factor on MicroRNA Expression Profile in Human Endothelial Progenitor Cells

2018 ◽  
Vol 27 (6) ◽  
pp. 1005-1009 ◽  
Author(s):  
Tongrong He ◽  
Ruohan Sun ◽  
Ying Li ◽  
Zvonimir S. Katusic
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Endothelial Progenitor ◽  
Regenerative Capacity ◽  
Proliferation And Differentiation ◽  
Guanylate Binding Protein

The mechanisms underlying proangiogenic function of brain-derived neurotrophic factor (BDNF) are not fully understood. The current study was designed to explore the microRNA (miRNA) profile in human early endothelial progenitor cells (EPCs, also referred to as CFU-Hill cells) treated with BDNF. Treatment of early EPCs with BDNF for 7 d significantly increased the colony formation of outgrowth endothelial cells. BDNF suppressed the expression of miR-4716-5p, miR-3928, miR-433, miR-1294, miR-1539, and miR-19b-1*. In contrast, BDNF significantly increased the levels of miR-432*, miR-4499, miR-3911, miR-1183, miR-4669, miR-636, miR-4717-3p, miR-4298, miR485-5p, and miR-181c. Since miR-433 has been reported to augment hematopoietic cells proliferation and differentiation, we examined the role of miR-433 in regenerative effects of BDNF. BDNF stimulated the protein expression of guanylate-binding protein 2 via the suppression of miR-433. However, the knockdown of miR-433 was not sufficient to significantly increase the number of outgrowth endothelial cell colonies, suggesting that modulation of miR-433 alone does not stimulate regenerative capacity of EPCs. In aggregate, our results also suggest that the effect of BDNF on regenerative function of EPCs may depend on complex changes in the expression of microRNAs.

scholarly journals Immune and Functional Role of Nitric Oxide in a Mouse Model of Respiratory Syncytial Virus Infection

2005 ◽  
Vol 191 (3) ◽  
pp. 387-395 ◽  
Author(s):  
James M. Stark ◽  
Amir M. Khan ◽  
Constance L. Chiappetta ◽  
Hasen Xue ◽  
Joseph L. Alcorn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Mouse Model ◽  
Respiratory Syncytial Virus Infection ◽  
Functional Role ◽  
Syncytial Virus
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