Bone marrow-derived MSC as endometrial stromal progenitor cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE20631 | GEO | 2010/03/31
SECONDARY ACCESSION(S): PRJNA124847
REPOSITORIES: GEO
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Project description:In the current study, we hypothesized that if bone-marrow derived MSC contribute to endometrial regeneration and are progenitors to hESF, their treatment with agents known to regulate hESF differentiation could promote their differentiation down the stromal fibroblast lineage. To this end, we treated bone marrow-derived MSC with estradiol (E2) and progesterone (P4), BMP2, and activators of the PKA pathway and investigated specific markers of hESF differentiation (decidualization). Furthermore, we investigated the transcriptome of these cells in response to cAMP and compared this to the transcriptome of hESF decidualized in response to activation of the PKA pathway. The data support that MSC can be differentiated down the hESF pathway, as evidenced by changes in cell shape and common expression of decidual markers and other genes important in hESF differentiation and function. Bone marrow-derived MSC were expanded in DMEM (high glucose) medium containing 10% fetal bovine serum, 1% penicillin and streptomycin. At 80% confluency MSC were trypsinized and plated at 5x103 cells/cm2 in 6cm plates. Nearly confluent cells were serumstarved overnight and thereafter treated for 0, 3, 7, 14 and 21 days in low-serum medium (2% FBS) with the following treatments: (a) 10nM E2/1mM P4; (b) 0.5mM or 1mM 8-Br-cAMP (cAMP); (c) 50nM or 100nM BMP-2; (d) 0.5mM and 1mM 8-Br-cAMP + BMP-2; (d) 0.5mM and 1mM 8-BrcAMP + BMP-2 + E2/P4; (e) 50nM or 100nM human FSH, with vehicle controls at each time point. Each experiment was conducted in duplicate and repeated at least 3 times. Media were changed every third day. Endpoints were prolactin (PRL) and IGF binding protein-1 (IGFBP1) mRNA, assessed by quantitative real-time RT-PCR, and protein in conditioned media, assessed by ELISA (see below), after 3, 7, 14 and 21 days of incubation. Immunostaining for vimentin, cytokeratin 7, and Oct-4 was performed before and after MSC treatments to assess the stromal lineage of MSC and their differentiation status. MSC expressed vimentin and did not express cytokeratin or Oct-4, independent of culture conditions or duration of culture or treatment. The morphological appearance of MSC under different treatment conditions was photographed using a Leica CTR 6500 microscope. Microarray analysis was performed with MSC, n=3, at t=0 (untreated, uncultured control), 14day vehicle control, and 14day treated with 8-Br-cAMP. Only high quality samples (RIN=9.1-10) were used for microarray analysis. Hybridization was performed with Affymetrix Human Gene 1.0 ST arrays.
2010-04-14 | E-GEOD-20631 | biostudies-arrayexpress
Project description:Maternal-stroma derived decidual cells are the single population in the canine placenta expressing the nuclear progesterone (P4) receptor (PGR), rendering them crucial for the maintenance of canine pregnancy. Indeed, decreased circulating P4 levels or blockage of PGR function with antigestagens (e.g., aglepristone), culminates in the termination of canine pregnancy. As an in vitro model for canine decidualization, dog uterine stromal (DUS; Graubner et al., 2017) cells can be decidualized in vitro with cAMP. The antigestagens aglepristone and mifepristone ablate the expression of decidualization markers in DUS cells (e.g., PGR, PRLR, IGF1 or PTGES). In order to study the mechanisms involved in feto-maternal communication during pregnancy and induction of parturition, the goal of the present work was to assess transcriptional changes mediated by decidualization and antigestagens-induced effects in decidualized DUS cells. Decidualization led to the upregulation of 1841 differentially expressed genes (DEGs, P < 0.01, FDR < 0.01) involved in cellular proliferation and adhesion, mesenchymal-epithelial transition, extracellular matrix organization, and vaso- and immunomodulation. The 1475 DEGs downregulated after decidualization were mostly associated with apoptosis and cell migration. In decidualized DUS cells, aglepristone modulated 1400 DEGs and mifepristone 1558 DEGs. Interestingly, only around half of the identified DEGs were modulated uniquely by one of the antigestagens. In both situations, however, PGR-blockage was associated with an inversion of decidualization-induced effects. Comparison between antigestagens-mediated effects and transcriptional changes in the canine placenta at term allowed the identification of 191 DEGs associated with cell proliferation and adhesion, vascularization and immune activity. These findings emphasize the importance of P4/PGR signaling for decidual cells function.
2022-12-28 | GSE213788 | GEO
Project description:The homeobox gene HOXA10 plays a key role in endometrial differentiation during embryogenesis and is abundantly expressed in the adult endometrium and decidual cells. In the adult endometrium the expression of HOXA10 is regulated by estrogen and progesterone and the levels are highest in the decidualized cells. We have shown that HOXA10 is required in the endometrial cells to maintain the decidual cell phenotype. In this study we aimed to determine the molecular mechanisms by which HOXA10 maintains the decidual phenotype and the other roles it might have in decidual physiology. In vitro decidualized human endometrial stromal cells were knocked down for HOXA10 using siRNA and gene expression profiles of the scrambled and HOXA10 siRNA transfected cells were compared at 24, 48 and 72 h post transfection. Several genes having multiple functions were found to be differentially expressed. We postulate that HOXA10 is required by the decidual cells to support immune cell differentiation, trophoblast invasion and cellular remodeling. In vitro decidualized priamry cultures of human endometrial strmal cells transfected with a siRNA againts HOXA10 or a scrambled siRNA. Cells harvested at 24, 48 and 72 h post transfection. Dual channel hybridization with dye swap design in biological replicates
2012-02-14 | E-GEOD-35801 | biostudies-arrayexpress
Project description:Gestation-matched endometrium was collected from women with ectopic pregnancy (EP) (n=11) and intrauterine pregnancies (IUP) (n=13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n=6) with non-decidualized samples (n=5), and b) the decidualized EP (n=6) with decidualization-matched IUP (n=6) samples.
2011-07-01 | E-MTAB-680 | biostudies-arrayexpress
Project description:Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterised endometrial assembloids, consisting of gland organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by inhibiting senescence and mesenchymal-epithelial transition, processes involved in endometrial breakdown and regeneration, respectively. Accelerated decidualization resulted in entrapment of co-cultured human blastocysts in a largely static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Together, our findings demonstrate that senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.
2021-03-08 | GSE168405 | GEO
Project description:The homeobox gene HOXA10 plays a key role in endometrial differentiation during embryogenesis and is abundantly expressed in the adult endometrium and decidual cells. In the adult endometrium the expression of HOXA10 is regulated by estrogen and progesterone and the levels are highest in the decidualized cells. We have shown that HOXA10 is required in the endometrial cells to maintain the decidual cell phenotype. In this study we aimed to determine the molecular mechanisms by which HOXA10 maintains the decidual phenotype and the other roles it might have in decidual physiology. In vitro decidualized human endometrial stromal cells were knocked down for HOXA10 using siRNA and gene expression profiles of the scrambled and HOXA10 siRNA transfected cells were compared at 24, 48 and 72 h post transfection. Several genes having multiple functions were found to be differentially expressed. We postulate that HOXA10 is required by the decidual cells to support immune cell differentiation, trophoblast invasion and cellular remodeling.
2012-02-14 | GSE35801 | GEO
Project description:Uterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and trans-differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by gamma-secretase inhibition resulted in significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1-dependant hypomorphic decidual phenotype. Microarray and pathway analysis, following Notch1 ablation, demonstrated significantly altered signaling repertoire. Concomitantly, hierarchical clustering demonstrated Notch1-dependent differences in gene expression. Uteri deprived of Notch1 signaling demonstrated decreased cellular proliferation; namely, reduced proliferation-specific antigen, Ki67, altered p21, cdk6, and cyclinD activity, and increased apoptotic-profile, augmented cleaved caspase-3, Bad, and attenuated Bcl2. Demonstrated here, the pre-implantation uterus relies on Notch signaling to inhibit apoptosis of stromal fibroblasts and regulate cell cycle progression, which together promotes successful decidualization. In summary, Notch1 signaling modulates multiple signaling mechanisms crucial for decidualization and we provide greater perspective to the coordination of multiple signaling modalities required during decidualization RNA samples from 3-5 separate mice were extracted. All mRNA quantities were normalized against 18S gene expression. Gene expression levels were measured by real-time RT-PCR SYBR Green analysis using the ABI Prism 7700 Sequence Detector System according to manufacturer’s instructions (Applied Biosystems).
2011-08-08 | E-GEOD-31244 | biostudies-arrayexpress
Project description:The pregnant decidua is infiltrated by many immune cells which are thought to originate in the bone marrow (BM) promoting pregnancy. In addition, BM-derived progenitor cells (BMDPCs) become non-hematopoietic endometrial cells. However, whether BMDPCs become non-immune decidual cells and their functional contribution to pregnancy were previously unknown. Here, we show that embryo implantation stimulates vast BMDPCs recruitment to decidua, where BMDPCs differentiate into non-hematopoietic stromal decidual cells. In addition, to determine the functional importance of BMDPCs to pregnancy, we used mice with endometrial stromal-specific defects precluding successful pregnancy. BM transplant (BMT) from wild-type (WT) into Hoxa11-/- mice, which lack decidualization, results in uterine transcriptional changes leading to stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. By contrast, BMT from Hoxa11-/- into WT mice induces pregnancy loss. Importantly, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that BMDPCs have a novel non-hematopoietic physiologic contribution to decidual stroma, thereby playing indispensable roles in pregnancy establishment and maintenance.
2019-12-01 | GSE104842 | GEO
Project description:To investigate the role of PRMT5 in decidualization, RNA-seq and gene expression profiling analysis was applied in control hEnSCs, GSK591 treated hEnSCs, decidualized hEnSCs and GSK591 treated decidualized hEnSCs
2022-08-20 | GSE205883 | GEO
Project description:Mesenchymal stromal cells (MSC) are ideal candidates for cell therapies, due to their immune-regulatory and regenerative properties. We have previously reported that lung-derived MSC are tissue-resident cells with lung-specific properties compared to bone marrow-derived MSC. Assessing relevant molecular differences between lung-MSC and bone marrow-MSC is important, given that such differences may impact their behavior and potential therapeutic use. Here, we present an in-depth mass spectrometry (MS) based strategy to investigate the proteomes of lung-MSC and bone marrow-MSC. The MS-strategy relies on label free quantitative data-independent acquisition (DIA) analysis and targeted data analysis using a MSC specific spectral library. We identified several significantly differentially expressed proteins between lung-MSC and bone marrow-MSC within the cell layer (352 proteins) and in the conditioned medium (49 proteins). Bioinformatics analysis revealed differences in regulation of cell proliferation, which was functionally confirmed by decreasing proliferation rate through Cytochrome P450 stimulation. Our study reveals important tissue-specific differences within proteome and matrisome profiles between lung- and bone marrow-derived MSC that may influence their behavior and affect the clinical outcome when used for cell-therapy.
2018-10-18 | PXD006419 | Pride