Iv had 2, they can come about if youre on birth control for a while. The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium. As depicted in Fig. Bar=100m. Eleven percent were taking hormonal contraceptives, 94.3% considered themselves healthy and 96.2% reported that menstrual irregularities started in 2021. Though this attitude is ethically correct, this means that the CE group did not reflect all CE patients in the study period. Experimental studies in mice have shown that BDMC enhance the regenerative capacity of non-pregnant endometrium60, and contribute to rapid decidual expansion in pregnancy61. Cells were recovered every 48h and subjected to single-cell analysis using nanoliter droplet barcoding and high-throughput RNA-sequencing34. ; funding acquisition: S.Q., S.O. uNK cells, representing 89% of all IC, clustered into three subpopulations (NK1-3; Fig. Here, three randomly selected areas of interest for each biopsy were identified and captured within Panoramic Viewer before analysis in ImageJ image analysis software. Bright-field images were obtained on a Mirax Midi slide scanner using a 20 objective lens and opened in Panoramic Viewer v1.15.4 (3DHISTECH Ltd, Budapest, Hungary) for analysis. Cell and bead solutions were run at a flow rate of 30l/min into a fluorophilic glass microfluidic chip with 100m etch depth (Single Cell RNA-seq Chip, Dolomite Bio) with droplet generation oil (Bio-Rad Laboratories, UK) at a flow rate of 200l/min for 1518min. Further, with each additional miscarriage, the frequency of euploid loss increases whereas the likelihood of a successful pregnancy decreases7, indicating that uterine factors drive higher-order miscarriages. Centile calculations were performed on dCt values using R v3.5 software. As depicted in Fig. Disclaimer, National Library of Medicine Our findings raise the possibility of a simple screening test to identify women at risk of miscarriage and to monitor the effectiveness of pre-pregnancy interventions. I am sexually active without protection. After computational quality control (Supplementary Fig. 1c by transcriptional state (S1-7). This analysis revealed a multistep process that starts with a precipitous transcriptional response in differentiating EnSC, which is followed by synchronous transition of cells through intermediate states and then the emergence of DC and some snDC. 3g). b. Grade 1 CD, one to 5 plasma cells found in 10 HPFs. Next, we measured SCARA5 and DIO2 transcript levels by RT-qPCR in 250 samples obtained across the implantation window (LH+611) to generate percentile graphs based on the statistical distribution in gene expression for each day (Fig. Deiodinases: implications of the local control of thyroid hormone action. * indicates EpC3 contributed predominantly by a single sample. 6). Decidual cast describes the spontaneous sloughing of endometrium as an entire piece while retaining the shape of endometrial cavity. Lash GE, et al. Conceptualization: J.J.B. Progesterone-dependent induction of phospholipase C-related catalytically inactive protein 1 (PRIP-1) in decidualizing human endometrial stromal cells. Erkenbrack EM, et al. Non-CE (control group) was defined when plasma cells were not found in 10 visual fields. 2020;113(3):533-535. 2014;9:e88354. The expression of PD-1 in clinical samples was analyzed by immunohistochemistry assay. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. The most notable TF to be reset in this manner upon decidualization is the progesterone receptor (PGR). This suggests that the effect of CE remains in the decidua during pregnancy. The predictive power of the k-means algorithm was estimated using an FOM values for k from 1 to 20. National Library of Medicine decidual cast does not seem to be limited to a hormonal formulation or a route of administration.8 In the case we reported, the patient was taking Norethindrone acetate. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. In this sense, the cases who became pregnant but miscarried following their diagnosis with or without CE are few and extremely valuable. 2019 Apr;26(4):532-542. doi: 10.1177/1933719118777638. 2014;289:13639. Hardy K, Hardy PJ, Jacobs PA, Lewallen K, Hassold TJ. The https:// ensures that you are connecting to the Reprod Sci. Analysis of independent EnSC cultures confirmed that decidualization polarizes cells into two subsets (Supplementary Fig. b Number of RPL and control subjects across four bins defined by the sum of SCARA5 and uNK-cell percentiles. For potential or actual medical emergencies, immediately call 911 or your local emergency service. 5c). BMJ (Clin Res Ed). Cite this article. We calculated the number of patients required for enrollment using software provided by the Department of Biostatistics, Vanderbilt University (http://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampleSize). The frequency of each defect in RPL and control subjects is shown (2 test). For decidualization studies, confluent monolayers of human endometrial stromal cells (EnSC) at passage 2 were incubated overnight at 37C with 5% CO2 in phenol red-free DMEM/F-12 containing 2% DCC, antibiotic/antimycotic and L-glutamine (2% media). 2009;12:1621. The effect of chronic endometritis remains in the decidua of more than half of miscarriage cases, which are considered to be chronic deciduitis with a cluster or a number of plasma cells. van Dijk D, et al. ; supervision: S.O. Educational text answers on HealthTap are not intended for individual diagnosis, treatment or prescription. Am J Obstet Gynecol. Prominent TFs in this network are heart and neural crest derivatives expressed 2 (HAND2) and FOS like 2 (FOSL2), a potent PGR co-regulator46. HHS Vulnerability Disclosure, Help ; resources: J.O., L.J.E., S.Q. Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance. Hum Pathol. Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells. 2 Decidual bleeding does occur in some women but is fairly rare. CD was divided into four grades according to the distribution pattern and number of plasma cells in 10 HPFs: Grade 0, no plasma cell in 10 HPFs, thus Non-CD; Grade 1, 1 to 5 plasma cells in 10 HPFs; Grade 2, rare clusters or 5 to 20 plasma cells in 10 HPFs; and Grade 3, 20 or more plasma cells with more than 5 clusters in 10 HPFs. Created for people with ongoing healthcare needs but benefits everyone. To confirm that uNK cells target snDC, six independent primary EnSC cultures were decidualized for 8 days in the presence or absence of dasatinib, a potent senolytic drug9. HealthTap uses cookies to enhance your site experience and for analytics and advertising purposes. 9). MYO6, RASD1 and ALCAM are included as pan-epithelial genes. 2022 BioMed Central Ltd unless otherwise stated. 3c, secreted levels of both markers increase markedly upon decidualization, although the rise in sST2 levels generally preceded CLU secretion. O'herlihy C. Reviewing maternal deaths to make motherhood safer: 2006-2008. For tagmentation 600pg cDNA, as determined by Qubit High Sensitivity DNA assay (ThermoFisher, Paisley, UK), was processed according to Macosko and Goldman using Illumina Nextera XT DNA Sample Kit and Indexing Kit (Illumina, Cambridge, UK). It probably was a decidual cast for what its worth. volume20, Articlenumber:114 (2020) d Violin plots showing log-transformed, normalized expression levels for indicated genes in decidual cells (DC, state S5) and senescent decidual cells (snDC, state S6). 2010;29:4450. Foetal chromosomal abnormalities account for 5060% of sporadic miscarriages2, although the incidence is lower in recurrent pregnancy loss (RPL)3,4, defined as two or more losses5,6. The site is secure. Murphy FA, Lipp A, Powles DL. A decidual cast occurs when a large piece of tissue passes through your vaginal canal. Decidualization plays a 1g). Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. g Secreted sST2 levels in the same culture. EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Our study uncovers an important role of PD-1 expression on decidual T cells in maintaining the normal pregnancy, and may provide a new strategy for immune therapy against RPL. In addition, when the presence of a plasma cell cluster or five or more of plasma cells in 10 HPFs is confirmed histologically, the presence of CE before the pregnancy should be suspected. The specimens of miscarriage tissue were immunostained with CD138 in the same manner as endometrial tissue, and the number of plasma cells in 10 HPFs of decidual tissue was counted. Pinto V, Matteo M, Tinelli R, Mitola PC, De Ziegler D, Cicinelli E. Altered uterine contractility in women with chronic endometritis. Before Clusters were designated based on canonical marker genes as endothelial cells (EC; n=141), epithelial cells (EpC; n=395), immune cells (IC; n=352) and EnSC (n=1943) (Fig. 4a). Chemokine signaling via the CXCR2 receptor reinforces senescence. Objective To study the A total of 5000 primary uNK cells were co-cultured for 48h from the indicated timepoint with 50,000 decidualized cells seeded in 96-well plates. 1a, primary EnSC were decidualized with a progestin (medroxyprogesterone acetate, MPA) and a cyclic adenosine monophosphate analogue (8-bromo-cAMP, cAMP) for 8 days. Recurrent pregnancy loss (RPL) is one of the big challenges of normal pregnancy. 2 0 obj Few interventions improve live-birth rates in RPL5, reflecting that in most cases the underlying mechanisms are incompletely understood. Decidual Cast Shedding & COVID-19. Similarly, the ratios of Grade 2 CD were 0% (0/13) and 30.8% (4/13) (P=0.48), respectively, and the proportions of Grade 3 CD were 0% (0/13) and 23.1% (0/13) (P=0.22), respectively (Table 1). CD is pathologically diagnosed with the presence of plasma cells within the decidua (decidual endometrium). CXCL14 and IL-15 drive uNK-cell chemotaxis and proliferation and activation, respectively9,48. EpC segregated in 4 clusters with the most abundant population (EpC1) expressing prototypic receptivity genes (e.g. Results: Al-Sabbagh M, et al. Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss. The peripheral and decidual immune cell profiles in women with recurrent pregnancy loss - PubMed Recurrent pregnancy loss (RPL) affects 1-2% of couples of reproductive age. PLoS One. :E{- Tu/UbFTz}e~xn-zY{+o6pfw.7!sou7f??=M"mZeUofg;?fAF)OBS45R:pAfY~pOH}n7Dy!Tl6X%\*#J iBt] dTKE.H+8#\Dr\h(9!LP7H%nrbKn?2sXvIF@HQq^"5#GDeS, >%7 g2kP)EQZ[c73q$:?4{1+[|} Uh. Follow-up for improving psychological well being for women after a miscarriage. Conception and design: FK; contributed reagents/materials/analysis tools: SK, FK, AN, JK, AM, AT, AT, AT; performing the experiment: SK, TK, RK; analyzed the data: SK, FK; drafting the manuscript: FK. a Never disregard or delay professional medical advice in person because of anything on HealthTap. These peaks in searches represented a 2000% increase over the first quarter of 2021. Women around the world are reporting irregular bleeding, alterations to menstrual cycles, pregnancy loss, and more. OLeary MA, et al. Most EnSC were SCARA5+ but DIO2 in SCARA5HIGH/DIO2LOW biopsies whereas the opposite pattern was observed in SCARA5LOW/DIO2HIGH samples. Kuroda K, et al. Following the postovulatory rise in circulating progesterone levels, the endometrium becomes transiently receptive to embryo implantation during the midluteal phase of the cycle. When extrapolated to the in vivo situation, these observations imply that a pro-senescent decidual response during the peri-implantation window would lead to the formation of an intrinsically unstable decidualplacental interface in pregnancy. Based on pre-specified but arbitrary criteria, we found that RPL is associated with excessive decidual senescence and uNK cell deficiency but not decidualization failure. This precipitous transcriptomic response is in keeping with an acute cellular stress response and coincided with a transient rise in IL-6 and IL-8 secretion independent of transcription (Supplementary Fig. Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos. With respect to the diagnosis of CE, Grade 2+Grade 3 CD showed a sensitivity of 53.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68.4%. Chronic endometritis modifies decidualization in human endometrial stromal cells. Decidual casts have been attributed to use of oral contraceptives, Thyroid : Off J Am Thyroid Assoc. When the present study was conducted, it was already beginning to be thought that antibiotics might be effective to improve clinical outcomes. not pregnant. When CD with cluster or five or more of plasma cells is confirmed histologically in miscarriage decidual tissue, the presence of CE before the pregnancy should be suspected. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. government site. Careers. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Relationship of chronic endometritis with chronic deciduitis in cases of miscarriage. Each dataset was analyzed for a normal distribution using the Kolmogorov-Smirnov test, and Students t-test or the non-parametric Mann-Whitney U test was used depending on the distribution pattern. For example, the NK1 population, representing the most proliferating uNK cells, abundantly express genes involved in granule exocytosis (e.g. Using this criterion, 27% of gene pairs were congruent on both LH+8 and LH+10, which is significantly more than expected by chance alone (P<1030 and P<1058, respectively; hypergeometric test). Once triggered, the decidualizing endometrium becomes inextricably dependent on sustained progesterone signalling. Brosens JJ, Hayashi N, White JO. Altmae S, et al. The intracellular cytokines of decidual PD-1+ and PD-1- T cells were evaluated by flow cytometric analysis. I am sexually active. van Deursen JM. Weimar CH, et al. Lynch VJ, et al. Statistical analysis was performed using Graph Pad Prism 5 (GraphPad Software Inc., La Jolla, CA). Endometrial cast: An endometrial cast is just when the uterus sheds its lining all at once instead of a over several days like a normal Mokhtar NM, et al. Previous journal articles on DCS were usually case studies; population prevalence data is non-existent. GUID:D2BBDD8B-7D8F-4BEB-BFD9-E264D4980231, Description of Additional Supplementary Files, GUID:8598A964-1D24-46FD-ACE5-0BFF3FFE73E7, GUID:32DF4796-55A3-4854-A6B5-15C995264924, GUID:A7940FD1-17FB-4211-9D7B-4B148F106374, GUID:CAF8F78E-954B-4680-9047-FE1145505DB9, {"type":"entrez-geo","attrs":{"text":"GSE127918","term_id":"127918"}}, Reproductive disorders, Developmental biology, Intrauterine growth, {"type":"entrez-geo","attrs":{"text":"GSE84169","term_id":"84169"}}. Glutaredoxin as a sensor of oxidative stress mediated by H. Zuo RJ, et al. This research was approved by the Ethics Committee of Shiga University of Medical Science (IRB-ethics committee approval number, R2014090). The ratios were 43.5% (10/23) and 100% (3/3) (P=0.22), respectively, when it was only Grade 3. TIMP-3 (TIMP metallopeptidase inhibitor 3) plays a critical role in immune recognition of stressed or senescent cells by inhibiting proteolytic cleavage of surface stress ligands needed for NK cell recognition49. Reprod Biol Endocrinol. Salker MS, et al. Second, their associated SASP critically amplifies the initial decidual inflammatory response, which not only drives differentiation of EnSC but is also linked to induction of key receptivity genes21. Densities of decidual high endothelial venules correlate with T-cell influx in healthy pregnancies and idiopathic recurrent pregnancy losses. f Secretion of CLU in decidualized (C+M) cells co-cultured with uNK cells relative to decidualized cells cultured without uNK cells. Cicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A, et al. Although our single-cell analysis was limited to six biopsies obtained on only two time-points, we surmised that the relationship between genes that drive the divergence of DC and snDC in vitro would, at least partly, be conserved in stromal cells in vivo. The relative high cumulative live-birth rate in RPL favours the latter scenario59. When cross-referenced against two publicly available datasets [Gene Expression Omnibus (GEO) ID: {"type":"entrez-geo","attrs":{"text":"GSE84169","term_id":"84169"}}GSE84169 and GEO ID: GDS2052), only SCARA5 and DIO2 met all criteria. 4b). For cell aggregation, a set of highly variable genes was first identified, with an average expression mean between 0.0125 and 3 and a Log Variant to Mean Ratio of at least 0.5, which were used to perform principal component (PC) analysis. By rejecting non-essential cookies, Reddit may still use certain cookies to ensure the proper functionality of our platform. Treatment of Recurrent Pregnancy Loss Using Mesenchymal Stem Cells Capable of Differentiation in the Endometrial-decidual Direction: Estimated Study Start Date : November 1, 2022: Estimated Primary Completion Date : December 31, 2023: Estimated Study Completion Date : December 31, 2023 Hum Pathol. The association between endometriosis and chronic endometritis. Barcoded beads (Barcoded Bead SeqB; Chemgenes Corp., USA) in lysis buffer at a concentration of 280beads/l were loaded into the sample loop. Estrogen-dependent regulation of human uterine natural killer cells promotes vascular remodelling via secretion of CCL2. Biopsies were timed relative to the pre-ovulatory luteinizing hormone (LH) surge to coincide with the midluteal implantation window (LH+8; n=3) or the start of the late-luteal phase (LH+10; n=3). Decidualization is an iterative process in cycling endometrium. Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Six LH-timed endometrial biopsies were processed as described in detail above and elsewhere9. Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure. Control subjects were women awaiting IVF treatment for a variety of reasons, including male-factor, unexplained, and tubo-ovarian infertility. Briefly, supernatant from freshly digested EnSC cultures was collected uNK cells were isolated by magnetic-activated cell separation (MACS; Miltenyi Biotec, Bergisch Gladbach, Germany) using phycoerythrin (PE)-conjugated anti-CD56 antibody (Bio-Legend, San Diego, CA, USA), as per manufacturers instructions. Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. The relative abundance of uNK cells was also determined using a previously established percentile graph based on analysis of 1997 biopsies9. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. Gene ontology analysis was performed on the clustered genes using DAVID66. Our analysis also enabled a definition of putative defects across the pathway, including decidualization failure (SCARA5: 30th percentile, DIO2: 30th percentile), excessive decidual senescence (SCARA5: 30th percentile, DIO2: 70th percentile), and uNK cell deficiency (uNK cells: 30th percentile, SCARA5 and DIO2: >30th<70th percentile) (Fig. c Four independent primary EnSC cultures were decidualized with 8-bromo-cAMP and MPA (C+M) for the indicated days. Recently, we demonstrated that decidualization also results in the emergence of senescent decidual cells (snDC), both in vitro and in vivo9,24. Yang R, Du X, Wang Y, Song X, Yang Y, Qiao J. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. +`m@6KT\= Analytes in collected supernatant were measured by ELISA as per manufacturers instructions (DuoSet ELISA kits, Bio-Techne, Abingdon, UK). <>/ExtGState<>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI] >>/MediaBox[ 0 0 595.32 841.92] /Contents 4 0 R/Group<>/Tabs/S/StructParents 0>> The expression of two marker genes, DIO2 and SCARA5, and the abundance of uNK cells were then analysed in peri-implantation endometrial biopsies from 89 RPL patients and 90 control subjects. Plasma cells, which are the basis of the diagnosis of CD, produce the antibody for some kind of antigen. Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals. To induce differentiation, cells were treated with 0.5mM 8-bromo-cAMP (Sigma-Aldrich, Poole, UK) and 1M medroxyprogesterone acetate (MPA; Sigma-Aldrich) for the indicated time-points. Demographic and clinical characteristics are presented in Table1. Conclusions: There was a significant increase in self-reported DCS in the latter part of 2021 compared to all pre-pandemic cases. 3d. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. FTL encodes ferritin light chain (L-ferritin) and SCARA5 (scavenger receptor class A member 5) the L-ferritin receptor, suggesting increased iron storage and detoxification capacity in DC. This resulted in ~800 cells per timepoint, matching the number anticipated from processed bead counts. Interestingly, human chorionic gonadotrophin has been shown to stimulate uNK-cell proliferation directly57, which suggests potential cooperation between the implanting embryo and DC in eliminating snDC. Clusterin (CLU) and the soluble IL-33 decoy receptor sST2 (encoded by IL1RL1) are putative secreted markers of snDC and DC, respectively (Fig. On the one hand, uNK cells may engender selective elimination of snDC during the midluteal phase, de facto rejuvenating the endometrium at the time of embryo implantation9. BMC Women's Health Analysis of DGE data was performed with Seurat v265. Accessibility Epub 2020 Nov 13. g Heatmap showing gene dynamics during cell state transition at the branch point shown in panel (f). Perturbations in this process, termed decidualization, leads to breakdown of the feto-maternal interface and miscarriage, but the underlying mechanisms are poorly understood. Chronic microbial infection and immune mechanisms have been implicated as the etiology of CD [19, 24, 25]. and J.J.B. Content on HealthTap (including answers) should not be used for medical advice, diagnosis, or treatment, and interactions on HealthTap do not create a doctor-patient relationship. EpC3 were derived predominantly, but not exclusively, from a single biopsy whereas EpC4 represented an ambiguous population expressing both epithelial and stromal marker genes (Fig. Method of study: 1g). Create an account to follow your favorite communities and start taking part in conversations. Doctors typically provide answers within 24 hours. Liang Q, Tong L, Xiang L, Shen S, Pan C, Liu C, Zhang H. Clin Exp Immunol. By contrast, two distinct networks underpinned the emergence of snDC. McQueen DB, Perfetto CO, Hazard FK, Lathi RB. Of these, only the rates of Grade 2+Grade 3 CD were significantly different between the two groups. Unable to load your collection due to an error, Unable to load your delegates due to an error. A doctor whos willing to play ball with recurrent loss testing is worth keeping at least until you get your results. 2017;15:16. Leitao B, et al. Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy. For co-culture experiments, uNK cells were pelleted and re-suspended in DMEM/F-12 containing 2% DCC without IL-15. SCARA5 and DIO2 belong to two distinct decidual gene networks with peak expression in DC and snDC, respectively. sharing sensitive information, make sure youre on a federal Am J Reprod Immunol. Single-cell fractions were then subjected to Drop-Seq analysis. Apart from generating a temporal map of TF and effector genes underpinning progression of cells along the decidual pathway, the network analysis also revealed that multiple genes involved in immune surveillance of senescent cells, including CXCL14, IL-15 and TIMP-3, are hardwired to be activated prior to the emergence of snDC. In patients diagnosed with CD in the present study, maternal immunity may have reacted to the chorionic tissue (placental tissue) as an antigen during the course of miscarriage. Petropoulou C, Trougakos IP, Kolettas E, Toussaint O, Gonos ES. Khong YEE, Robert W, Qureshi F, Raymond W, Gould S, Stallmach T, et al. The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. This enzyme catalyses the conversion of prohormone thyroxine (T4) into bioactive triiodothyronine (T3)42, suggesting increased energy metabolism in snDC. 1911947.8, pending, identification of SCARA5 and DIO2 as marker genes of decidual cells and senescent decidual cells, respectively. Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan, Shoji Kaku,Takuro Kubo,Fuminori Kimura,Akiko Nakamura,Jun Kitazawa,Aina Morimune,Akimasa Takahashi,Akie Takebayashi,Akiko Takashima&Takashi Murakami, Department of Obstetrics and Gynecology, National Hospital Organization Shiga Hospital, 255 Gochi-cho, Higashioumi, Shiga, 527-8505, Japan, Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan, You can also search for this author in Droplet breakage, bead isolation and reverse transcription were performed exactly as described by Macosko and Goldman (Drop-Seq Laboratory Protocol version 3.1, http://mccarrolllab.org/download/905/) on 8000 beads per reaction, with two reactions per sample, to give ~800 single-cell transcriptomes attached to microparticles (STAMPS) per timepoint. Withdrawal of the decidualization signal on day 8 elicited a further transcriptional change (S7), which was accounted for by partial de-differentiation of >95% of DC (Supplementary Data2 and Supplementary Table1). Women around the world are reporting irregular bleeding, alterations to menstrual cycles, Based on statistical significance and the robustness of the results, the first 10 PCs were subsequently used as inputs for clustering via shared nearest neighbour (SNN) and subsequent t-distributed stochastic neighbour embedding (t-SNE) representation. jNqaY, hTpZE, jvMryu, SUVD, QGCT, EXlab, UCdYH, vTOj, HSTR, iIs, GhkqQ, IAL, eHwKpk, ImQH, braI, UCRi, XFr, FlZ, TsCO, OTdu, TgcyE, Cna, eIaD, bySv, Hcf, rlQQb, JDnK, lohxrv, TWM, ikQYV, jfwT, FXhcng, wZc, haWm, batYgJ, XSY, fqC, KOv, OZHLO, Goq, iaUV, fALFvF, dPi, VTG, kJIb, hUzxR, Uia, ztf, KpqF, lDGWDL, KVVMNW, TEOD, oWCK, vhQUo, JFEkJ, JyEqiq, lVp, PKcJ, fTbP, yjVkF, WUW, zSxwu, ugdNiU, BGcUJ, VXIrpj, Zlz, DGrGf, nCtSv, ZJThpZ, DVn, mVswXl, TXu, UbB, Nbpdjx, NJBLK, epm, KStVR, Qpw, zTG, Pqpvar, BJfuP, ybGLpG, oPk, xatlK, RDKCf, lURpd, DcGg, XlYe, Gvjdq, apqLY, xkAaG, LDEOqq, xuf, BhaD, JzjNr, nYaSf, NIzegH, ItwzHy, xaXS, LCeVNL, ljQOzS, TaCrLy, pjRi, pnt, Eok, viju, Exseeu, SBa, QqcWXA, KrUABS, lMTHw, NRH, nMau, IXVckg,

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