Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization

Abstract

Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization. Physiol Genomics 7: 135-148, 2001. First published September 21, 2001; 10.1152/physiolgenomics.00061.2001.-Human decidual fibroblasts undergo a differentiative commitment to the acquisition of endocrine, metabolic, and structural cell functions in a process known as decidualization. Decidualization is critical for embryo implantation and placental function. We characterized gene expression pattern kinetics during decidual fibroblast differentiation by microarray analysis. Of 6,918 genes analyzed, 121 genes were induced by more than twofold, 110 were downregulated, and 50 showed biphasic behavior. Dynamically regulated genes were could be fit into nine K-means algorithm-based kinetic pattern groups, and by biologic classification, into five categories: cell and tissue function, cell and tissue structure, regulation of gene expression, expressed sequence tag (EST), and "function unknown." Reprogramming of genes within specific functional groups and gene families was a prominent feature that consisted of simultaneous induction and downregulation of a set of genes with related function. We previously observed a conceptually similar process during fetal trophoblast differentiation, in which the same phenomena applied to different genes. Of the 569 dynamically regulated genes regulated by either model, only 81 of these were in common. These results suggest that reprogramming of gene expression within focused functional categories represents a fundamental aspect of cellular differentiation.

Effect of low-dose mifepristone administration on day 2 after ovulation on transcript profiles in implantation-stage endometrium of rhesus monkeys

“…Although most of the novel gene products that were observed to be affected in the present study were already known to be involved in endometrial functionality from previous studies (see Table 7 for details), we are reporting for the first time that these were differentially regulated by high-affinity antiprogestin resulting in implantation failure in the rhesus monkey. Additionally, the observation in the present study that while a cohort of gene expression was consistent between days 4 and 6 after ovulation in a fecund cycle, a group of genes showed specific repression and derepression in the time course makes us to assume that endometrial receptivity in the rhesus monkey is associated with categorical reprogramming in endometrial tanscriptomics as observed in human endometrial fibroblasts in vitro (Brar et al 2001), human placental villous cytotrophoblasts in vitro , and mouse decidual cells (Kashiwagi et al 2007). We believe that elucidation of the time course pattern of endometrial receptivity associated transcriptomic networks will be beneficial to clinical sciences in improvising strategies to assist the establishment of pregnancy.…”

Global Analysis of Genes Regulated by HOXA10 in Decidualization Reveals a Role in Cell Proliferation.

“…During this time, numerous genes are regulated in a time-dependent manner as previously shown by others (Brar et al, 2001;Tierney et al, 2003). In order to elucidate the role of HOXA10 during decidualization, HOXA10 was first silenced in HESCs using siRNA and subsequently treated with H + cAMP for 48 h. This technique efficiently knocked down HOXA10 mRNA and protein expression (Fig.…”

“…Other microarray studies have identified the genes that are most prominently regulated during decidualization and have provided insight to types of transformations that occur (Brar et al, 2001;Tierney et al, 2003;Takano et al, 2007). While identification of a function for a particular gene during this process in human cells has been a challenge, techniques involving gene silencing in combination with microarray analysis with the use of bioinformatics tools have made it feasible to define a role for a particular gene of interest during decidualization.…”

“…The 50 most highly induced and repressed genes are shown in Supplementary Table S2. Many of these genes have previously been reported to be decidua-specific (Brar et al, 2001;Tierney et al, 2003;Takano et al, 2007). Of the 2361 decidua-specific genes, 258 were significantly up-regulated by HOXA10 knockdown and 236 transcripts were significantly down-regulated by more than 1.5-fold, totaling 494 genes that were regulated by HOXA10 during decidualization (Supplementary Table S3).…”

NODAL signaling components regulate essential events in the establishment of pregnancy

“…LEFTYA and LEFTYB were demonstrated by microarray analysis and verified by northern blot to be one of the most abundantly induced factors in the decidua that supports implantation (Brar et al 2001). Moreover, expression of the LEFTY processing enzyme SPC5/6 was significantly increased within HESC during decidualization in vitro (Okada et al 2005).…”