Lymphoid committed CD34+lin-CD10+CD24- progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid committed progenitors and CD34+Lin-CD10- non lymphoid progenitors in 11 allo-HSCT patients having (n=5) or not developed (n=6) grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major deregulated pathways included protein synthesis, energy production, cell cycle regulation and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery and cell cycle (CDK6) were over-expressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid committed progenitors in absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPases activity. In all, we show that circulating lymphoid committed progenitors undergo profound changes in metabolism favoring cell proliferation, energy production and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from bone marrow.
Alterations of circulating lymphoid committed progenitor cellular metabolism after allogeneic stem cell transplantation in humans.
Disease, Disease stage, Subject
View SamplesHuman placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion.
Transcriptome analysis of PPARγ target genes reveals the involvement of lysyl oxidase in human placental cytotrophoblast invasion.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesAnalysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesMyasthenia gravis (MG) is a relatively rare autoimmune neuromuscular disorder. Monozygotic twin studies indicate that discordance rate in MG is about 70-60%, suggesting that despite identical DNA unknown factors contribute to disease development. The aim of the current study was to identify novel disease-associated genes in purified monocytes, including both genes associated with predisposition or with disease course, using the unique model of MZ twins. Thus the transcriptome and methylome were compared between twins discordant and concordant for the diseases, as well as MG singletons, and healthy controls. Several transcripts associated with immune homeostasis and inflammation resolution were highlighted in the current study. High similarity between the healthy and the MG discordant twins found, suggest that genetic predisposition may have a stronger contribution then previously assumed. In addition, results suggest that numerous small changes in expression and DNA methylation might contribute to disease onset making it more difficult to pick up
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesAnalysis of B16 tumor microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchastrated the immune reponse triggered in presence of tumors
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesIn order to identify pre-conceptional endometrial dysregulations, we compared the endometrial expression between fertile and IF and RM patients
Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages.
Sex, Specimen part
View SamplesAnalysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo.
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesAnalysis of weakly immunogenic, B16 tumor environment at gene expression level after Treg depletion
No associated publication
Age, Specimen part
View Samples