scholarly journals Changes in cell cycle and extracellular matrix gene expression during placental development in deer mouse (Peromyscus) hybrids

2007 ◽  
Vol 19 (5) ◽  
pp. 695 ◽  
Author(s):  
Amanda R. Duselis ◽  
Craig Obergfell ◽  
Jennifer A. Mack ◽  
Michael J. O'Neill ◽  
Quang K. Nguyen ◽  
...  

Crosses between two species of the rodent genus Peromyscus produce defects in both growth and development. The defects are pronounced in the hybrid placentas. Peromyscuys maniculatus (strain BW) females mated to P. polionotus (strain PO) males produce placentas half the size of the parental species, as well as growth-retarded embryos. In contrast, PO females mated to BW males result in defective conceptuses that display embryonic and placental overgrowth. These ‘parent-of-origin’-dependent phenotypes are consistent with previous studies that demonstrated altered expression of imprinted genes and genetic linkage of the overgrowth phenotypes to imprinted domains. In the present study, we take a broader approach in assessing perturbations in hybrid placental gene expression through the use of Mus musculus cDNA microarrays. In verifying classes of genes identified in microarray screens differentially regulated during hybrid placental development, we focused on those influencing the cell cycle and extracellular matrix (ECM). Our work suggests that cell cycle regulators at the G1/S phase check-point are downregulated in the large hybrid placenta, whereas the small hybrid placenta is more variable. The ECM genes are typically downstream targets of cell cycle regulation and their misregulation is consistent with many of the dysmorphic phenotypes. Thus, these data suggest imbalances in proliferation and differentiation in hybrid placentation.

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2214
Author(s):  
Nina-Naomi Kreis ◽  
Alexandra Friemel ◽  
Lukas Jennewein ◽  
Samira Catharina Hoock ◽  
Anna Elisabeth Hentrich ◽  
...  

Preeclampsia (PE), a gestational hypertensive disease originating from the placenta, is characterized by an imbalance of various cellular processes. The cell cycle regulator p21Cip1/CDKN1A (p21) and its family members p27 and p57 regulate signaling pathways fundamental to placental development. The aim of the present study was to enlighten the individual roles of these cell cycle regulators in placental development and their molecular involvement in the pathogenesis of PE. The expression and localization of p21, phospho-p21 (Thr-145), p27, and p57 was immunohistochemically analyzed in placental tissues from patients with early-onset PE, early-onset PE complicated by the HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome as well as late-onset PE compared to their corresponding control tissues from well-matched women undergoing caesarean sections. The gene level was evaluated using real-time quantitative PCR. We demonstrate that the delivery mode strongly influenced placental gene expression, especially for CDKN1A (p21) and CDKN1B (p27), which were significantly upregulated in response to labor. Cell cycle regulators were highly expressed in first trimester placentas and impacted by hypoxic conditions. In support of these observations, p21 protein was abundant in trophoblast organoids and hypoxia reduced its gene expression. Microarray analysis of the trophoblastic BeWo cell line depleted of p21 revealed various interesting candidate genes and signaling pathways for the fusion process. The level of p21 was reduced in fusing cytotrophoblasts in early-onset PE placentas and depletion of p21 led to reduced expression of fusion-related genes such as syncytin-2 and human chorionic gonadotropin (β-hCG), which adversely affected the fusion capability of trophoblastic cells. These data highlight that cell cycle regulators are important for the development of the placenta. Interfering with p21 influences multiple pathways related to the pathogenesis of PE.


2019 ◽  
Author(s):  
Alberto Perez-Posada ◽  
Omaya Dudin ◽  
Eduard Ocaña-Pallarès ◽  
Iñaki Ruiz-Trillo ◽  
Andrej Ondracka

AbstractProgression through the cell cycle in eukaryotes is regulated on multiple levels. The main driver of the cell cycle progression is the periodic activity of cyclin-dependent kinase (CDK) complexes. In parallel, transcription during the cell cycle is regulated by a transcriptional program that ensures the just-in-time gene expression. Many core cell cycle regulators are present in all eukaryotes, among them cyclins and CDKs; however, periodic transcriptional programs are divergent between distantly related species. In addition, many otherwise conserved cell cycle regulators have been lost and independently evolved in yeast, a widely used model organism for cell cycle research. To gain insight into the cell cycle regulation in a more representative opisthokont, we investigated the cell cycle regulation at the transcriptional level of Capsaspora owczarzaki, a species closely related to animals. We developed a protocol for cell cycle synchronization in Capsaspora cultures and assessed gene expression over time across the entire cell cycle. We identified a set of 801 periodic genes that grouped into five clusters of expression over time. Comparison with datasets from other eukaryotes revealed that the periodic transcriptional program of Capsaspora is most similar to that of animal cells. We found that orthologues of cyclin A, B and E are expressed at the same cell cycle stages as in human cells and in the same temporal order. However, in contrast to human cells where these cyclins interact with multiple CDKs, Capsaspora cyclins likely interact with a single ancestral CDK1-3. Thus, the Capsaspora cyclin-CDK system could represent an intermediate state in the evolution of animal-like cyclin-CDK regulation. Overall, our results demonstrate that Capsaspora could be a useful unicellular model system for animal cell cycle regulation.Author’s summaryWhen cells reproduce, proper duplication and splitting of the genetic material is ensured by cell cycle control systems. Many of the regulators in these systems are present across all eukaryotes, such as cyclin and cyclin-dependent kinases (CDK), or the E2F-Rb transcriptional network. Opisthokonts, the group comprising animals, yeasts and their unicellular relatives, represent a puzzling scenario: in contrast to animals, where the cell cycle core machinery seems to be conserved, studies in yeasts have shown that some of these regulators have been lost and independently evolved. For a better understanding of the evolution of the cell cycle regulation in opisthokonts, and ultimately in the lineage leading to animals, we have studied cell cycle regulation in Capsaspora owczarzaki, a unicellular amoeba more closely related to animals than fungi that retains the ancestral cell cycle toolkit. Our findings suggest that, in the ancestor of Capsaspora and animals, cyclins oscillate in the same temporal order as in animals, and that expansion of CDKs occurred later in the lineage that led to animals.


1993 ◽  
Vol 43 (6) ◽  
pp. 1219-1225 ◽  
Author(s):  
Leslie A. Bruggeman ◽  
Jill A. Pellicoro ◽  
Elizabeth A. Horigan ◽  
Paul E. Klotman

2021 ◽  
pp. 100069
Author(s):  
Fabio Sacher ◽  
Christian Feregrino ◽  
Patrick Tschopp ◽  
Collin Y. Ewald

2018 ◽  
Author(s):  
Nicholas L Panchy ◽  
John P. Lloyd ◽  
Shin-Han Shiu

AbstractThe collection all TFs, target genes and their interactions in an organism form a gene regulatory network (GRN), which underly complex patterns of transcription even in unicellular species. However, identifying which interactions regulate expression in a specific temporal context remains a challenging task. With multiple experimental and computational approaches to characterize GRNs, we predicted general and phase-specific cell-cycle expression in Saccharomyces cerevisiae using four regulatory data sets: chromatin immunoprecipitation (ChIP), TF deletion data (Deletion), protein binding microarrays (PBMs), and position weight matrices (PWMs). Our results indicate that the source of regulatory interaction information significantly impacts our ability to predict cell-cycle expression where the best model was constructed by combining selected TF features from ChIP and Deletion data as well as TF-TF interaction features in the form of feed-forward loops. The TFs that were the best predictors of cell-cycle expression were enriched for known cell-cycle regulators but also include regulators not implicated in cell-cycle regulation previously. In addition, ChIP and Deletion datasets led to the identification different subsets of TFs important for predicting cell-cycle expression. Finally, analysis of important TF-TF interaction features suggests that the GRN regulating cell cycle expression is highly interconnected and clustered around four groups of genes, two of which represent known cell-cycle regulatory complexes, while the other two contain TFs that are not known cell-cycle regulators (Ste12-Tex1 and Rap1-Hap1-Msn4), but are nonetheless important to regulating the timing of expression. Thus, not only do our models accurately reflect what is known about the regulation of the S. cerevisiae cell cycle, they can be used to discover regulatory factors which play a role in controlling expression during the cell cycle as well as other contexts with discrete temporal patterns of expression.


1997 ◽  
Vol 42 (6) ◽  
pp. 443-454 ◽  
Author(s):  
Shawn P. Macauley ◽  
Roy W. Tarnuzzer ◽  
Gregory S. Schultz ◽  
Nasser Chegini ◽  
Gregory E. Oxford ◽  
...  

2018 ◽  
Vol 40 (3) ◽  
pp. 223-233 ◽  
Author(s):  
Arcangela Anna Cera ◽  
Emanuele Cacci ◽  
Camilla Toselli ◽  
Silvia Cardarelli ◽  
Alessandra Bernardi ◽  
...  

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signaling pathways that reg­ulate NSC proliferation and differentiation remain poorly understood. Early growth response protein 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli. In our study, we aimed at testing how Egr-1 regulates adult NSCs derived from mouse SVZ and, in particular, the interplay between Egr-1 and the proliferative factor EGF. We demonstrate that Egr-1 expression in NSCs is induced by growth factor stimulation, and its level decreases after EGF deprivation or by using AG1478, an inhibitor of the EGF/EGFR signaling pathway. We also show that Egr-1 overexpression rescues the cell proliferation decrease observed either after EGF removal or upon treatment with AG1478, suggesting that Egr-1 works downstream of the EGF pathway. To better understand this mechanism, we investigated targets downstream of both the EGF pathway and Egr-1, and found that they regulate genes involved in NSC proliferation, such as cell cycle regulators, cyclins, and cyclin-dependent kinase inhibitors.


Sign in / Sign up

Export Citation Format

Share Document