259. Pluripotency genes in a marsupial, the tammar wallaby

2008 ◽  
Vol 20 (9) ◽  
pp. 59
Author(s):  
S. Frankenberg ◽  
A. J. Pask ◽  
M. B. Renfree

Markers of pluripotency and early differentiation in the early embryo have been extensively characterised in eutherian species, most notably the mouse. By comparison, mechanisms controlling pluripotency and early lineage specification have received surprisingly little attention in marsupials, which represent the second major infraclass of mammals. Early marsupial embryogenesis exhibits overt morphological differences to that of eutherians, however the underlying developmental mechanisms may be conserved. In order to characterise early marsupial development at the molecular level, we have identified, cloned and analysed expression of orthologueues of several eutherian genes encoding transcription factors and signalling molecules involved in regulating pluripotency and early lineage specification. These genes include POU5F1 (OCT4), SOX2, NANOG, FGF4, FGFR2, CDX2, EOMES, TEAD4, GATA6 and KITL and are all expressed at early stages of development in the tammar. In addition, we have identified and cloned tammar POU2, which has orthologueues in non-mammalian vertebrates. POU2 is a paralogue of POU5F1 – a master regulator of pluripotency in eutherians. Genomic analysis indicates that POU5F1 arose via gene duplication of POU2 before the monotreme-therian divergence. Both genes have persisted in marsupials and monotremes, while POU2 was lost early during eutherian evolution. Similar expression profiles of tammar POU5F1 and POU2 in early embryos and gonadal tissues suggest possible overlapping roles in the maintenance of pluripotency.

2010 ◽  
Vol 22 (9) ◽  
pp. 15 ◽  
Author(s):  
M. B. Renfree ◽  
S. R. Frankenberg ◽  
C. Freyer

In marsupials, the blastocyst forms as a single cell layer of cells. The marsupial blastocyst has no inner cell mass, so the 80–100 cell tammar embryo remains in diapause as a unilaminar blastocyst. All marsupials have a unilaminar stage, but what is unusual is that in the tammar the total cessation of cell division and cell metabolism lasts for 11 months each year. Marsupials are placental mammals. The yolk sac forms the definitive placenta up to birth. Only very few marsupials, such as the bandicoot, have a chorio-allantoic placenta, which supplements the placental functions of the yolk sac. However, the understanding how the unilaminar layer of trophoblast cells of the diapausing blastocyst become specified into placental and embryonic tissues has been an ongoing puzzle. To identify genes that do become differentially expressed in tammar development, we targeted the stage of the earliest appearance of the embryonic disc, at which the remainder of the blastocyst is then defined as trophoblast, as well as early cleavage stages. Intriguingly, we found no evidence for early differential expression of the canonical pluripotency genes POU5F1, SOX2 and NANOG, or of CDX2. By contrast, we found overt differential expression of GATA3, the closely related gene GATA2, and FGF4. This expression profile suggests that in the tammar, mechanisms regulating trophoblast- and pluriblast-specific expression of POU5F1, SOX2, NANOG and CDX2 are temporally secondary to those regulating GATA2 & -3 and FGF4 expression. Together, our results may signify the evolution of alternative mechanisms of early lineage specification in marsupials, or alternatively reveal a general hierarchy of signalling mechanisms that are masked in the relatively rapid and ‘compressed’ development of mice. The results of our ongoing study have important implications for understanding not only marsupial stem cells but the early development of all therian mammals.


2021 ◽  
Author(s):  
Shuang Li ◽  
Yan Shi ◽  
Yanna Dang ◽  
Bingjie Hu ◽  
Lieying Xiao ◽  
...  

Linker histone H1 binds to the nucleosome and is implicated in the regulation of the chromatin structure and function. The H1 variant H1FOO is heavily expressed in oocytes and early embryos. However, given the poor homology of H1FOO among mammals, the functional role of H1FOO during early embryonic development remains largely unknown, especially in domestic animals. Here, we find that H1FOO is not only expressed in oocytes and early embryos but granulosa cells and spermatids in cattle. We then demonstrate that the interference of H1FOO results in early embryonic developmental arrest in cattle using either RNA editing or Trim-Away approach. H1FOO depletion leads to compromised expression of critical lineage-specific genes at the morula stage and affects the establishment of cell polarity. Interestingly, H1FOO depletion causes a significant increase in expression genes encoding other linker H1 and core histones. Concurrently, there is an increase of H3K9me3 and H3K27me3, two markers of repressive chromatin and a decrease of H4K16ac, a marker of open chromatin. Importantly, overexpression of bovine H1FOO results in severe embryonic developmental defects. In sum, we propose that H1FOO controls the proper chromatin structure that is crucial for the fidelity of cell polarization and lineage specification during bovine early development.


2021 ◽  
Vol 9 (2) ◽  
pp. 348
Author(s):  
Florian Tagini ◽  
Trestan Pillonel ◽  
Claire Bertelli ◽  
Katia Jaton ◽  
Gilbert Greub

The Mycobacterium kansasii species comprises six subtypes that were recently classified into six closely related species; Mycobacterium kansasii (formerly M. kansasii subtype 1), Mycobacterium persicum (subtype 2), Mycobacterium pseudokansasii (subtype 3), Mycobacterium ostraviense (subtype 4), Mycobacterium innocens (subtype 5) and Mycobacterium attenuatum (subtype 6). Together with Mycobacterium gastri, they form the M. kansasii complex. M. kansasii is the most frequent and most pathogenic species of the complex. M. persicum is classically associated with diseases in immunosuppressed patients, and the other species are mostly colonizers, and are only very rarely reported in ill patients. Comparative genomics was used to assess the genetic determinants leading to the pathogenicity of members of the M. kansasii complex. The genomes of 51 isolates collected from patients with and without disease were sequenced and compared with 24 publicly available genomes. The pathogenicity of each isolate was determined based on the clinical records or public metadata. A comparative genomic analysis showed that all M. persicum, M. ostraviense, M innocens and M. gastri isolates lacked the ESX-1-associated EspACD locus that is thought to play a crucial role in the pathogenicity of M. tuberculosis and other non-tuberculous mycobacteria. Furthermore, M. kansasii was the only species exhibiting a 25-Kb-large genomic island encoding for 17 type-VII secretion system-associated proteins. Finally, a genome-wide association analysis revealed that two consecutive genes encoding a hemerythrin-like protein and a nitroreductase-like protein were significantly associated with pathogenicity. These two genes may be involved in the resistance to reactive oxygen and nitrogen species, a required mechanism for the intracellular survival of bacteria. Three non-pathogenic M. kansasii lacked these genes likely due to two distinct distributive conjugal transfers (DCTs) between M. attenuatum and M. kansasii, and one DCT between M. persicum and M. kansasii. To our knowledge, this is the first study linking DCT to reduced pathogenicity.


Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 298
Author(s):  
Despoina Konstantinou ◽  
Rafael V. Popin ◽  
David P. Fewer ◽  
Kaarina Sivonen ◽  
Spyros Gkelis

Sponges form symbiotic relationships with diverse and abundant microbial communities. Cyanobacteria are among the most important members of the microbial communities that are associated with sponges. Here, we performed a genus-wide comparative genomic analysis of the newly described marine benthic cyanobacterial genus Leptothoe (Synechococcales). We obtained draft genomes from Le. kymatousa TAU-MAC 1615 and Le. spongobia TAU-MAC 1115, isolated from marine sponges. We identified five additional Leptothoe genomes, host-associated or free-living, using a phylogenomic approach, and the comparison of all genomes showed that the sponge-associated strains display features of a symbiotic lifestyle. Le. kymatousa and Le. spongobia have undergone genome reduction; they harbored considerably fewer genes encoding for (i) cofactors, vitamins, prosthetic groups, pigments, proteins, and amino acid biosynthesis; (ii) DNA repair; (iii) antioxidant enzymes; and (iv) biosynthesis of capsular and extracellular polysaccharides. They have also lost several genes related to chemotaxis and motility. Eukaryotic-like proteins, such as ankyrin repeats, playing important roles in sponge-symbiont interactions, were identified in sponge-associated Leptothoe genomes. The sponge-associated Leptothoe stains harbored biosynthetic gene clusters encoding novel natural products despite genome reduction. Comparisons of the biosynthetic capacities of Leptothoe with chemically rich cyanobacteria revealed that Leptothoe is another promising marine cyanobacterium for the biosynthesis of novel natural products.


Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 500
Author(s):  
Jeeyong Lee ◽  
Junhye Kwon ◽  
DaYeon Kim ◽  
Misun Park ◽  
KwangSeok Kim ◽  
...  

LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness–related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi-Qiang Du ◽  
Hao Liang ◽  
Xiao-Man Liu ◽  
Yun-Hua Liu ◽  
Chonglong Wang ◽  
...  

AbstractSuccessful early embryo development requires the correct reprogramming and configuration of gene networks by the timely and faithful execution of zygotic genome activation (ZGA). However, the regulatory principle of molecular elements and circuits fundamental to embryo development remains largely obscure. Here, we profiled the transcriptomes of single zygotes and blastomeres, obtained from in vitro fertilized (IVF) or parthenogenetically activated (PA) porcine early embryos (1- to 8-cell), focusing on the gene expression dynamics and regulatory networks associated with maternal-to-zygote transition (MZT) (mainly maternal RNA clearance and ZGA). We found that minor and major ZGAs occur at 1-cell and 4-cell stages for both IVF and PA embryos, respectively. Maternal RNAs gradually decay from 1- to 8-cell embryos. Top abundantly expressed genes (CDV3, PCNA, CDR1, YWHAE, DNMT1, IGF2BP3, ARMC1, BTG4, UHRF2 and gametocyte-specific factor 1-like) in both IVF and PA early embryos identified are of vital roles for embryo development. Differentially expressed genes within IVF groups are different from that within PA groups, indicating bi-parental and maternal-only embryos have specific sets of mRNAs distinctly decayed and activated. Pathways enriched from DEGs showed that RNA associated pathways (RNA binding, processing, transport and degradation) could be important. Moreover, mitochondrial RNAs are found to be actively transcribed, showing dynamic expression patterns, and for DNA/H3K4 methylation and transcription factors as well. Taken together, our findings provide an important resource to investigate further the epigenetic and genome regulation of MZT events in early embryos of pigs.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zefang Sun ◽  
Jia Tan ◽  
Minqiong Zhao ◽  
Qiyao Peng ◽  
Mingqing Zhou ◽  
...  

AbstracttRNAs and tRNA-derived RNA fragments (tRFs) play various roles in many cellular processes outside of protein synthesis. However, comprehensive investigations of tRNA/tRF regulation are rare. In this study, we used new algorithms to extensively analyze the publicly available data from 1332 ChIP-Seq and 42 small-RNA-Seq experiments in human cell lines and tissues to investigate the transcriptional and posttranscriptional regulatory mechanisms of tRNAs. We found that histone acetylation, cAMP, and pluripotency pathways play important roles in the regulation of the tRNA gene transcription in a cell-specific manner. Analysis of RNA-Seq data identified 950 high-confidence tRFs, and the results suggested that tRNA pools are dramatically distinct across the samples in terms of expression profiles and tRF composition. The mismatch analysis identified new potential modification sites and specific modification patterns in tRNA families. The results also show that RNA library preparation technologies have a considerable impact on tRNA profiling and need to be optimized in the future.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xin Mao ◽  
Tracy Chaplin ◽  
Bryan D. Young

Sézary syndrome (SS) is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH) identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1) frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2) reduced SNP copy number at FAT gene (4q35) in 75% of SS cases, and (3) the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.


2016 ◽  
Vol 174 (6) ◽  
pp. R239-R247 ◽  
Author(s):  
Frederic Castinetti ◽  
Rachel Reynaud ◽  
Alexandru Saveanu ◽  
Nicolas Jullien ◽  
Marie Helene Quentien ◽  
...  

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations ofPOU1F1orPROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge.


Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 3005-3014 ◽  
Author(s):  
C. Takke ◽  
J.A. Campos-Ortega

During vertebrate embryonic development, the paraxial mesoderm becomes subdivided into metameric units known as somites. In the zebrafish embryo, genes encoding homologues of the proteins of the Drosophila Notch signalling pathway are expressed in the presomitic mesoderm and expression is maintained in a segmental pattern during somitogenesis. This expression pattern suggests a role for these genes during somite development. We misexpressed various zebrafish genes of this group by injecting mRNA into early embryos. RNA encoding a constitutively active form of notch1a (notch1a-intra) and a truncated variant of deltaD [deltaD(Pst)], as well as transcripts of deltaC and deltaD, the hairy-E(spl) homologues her1 and her4, and groucho2 were tested for their effects on somite formation, myogenesis and on the pattern of transcription of putative downstream genes. In embryos injected with any of these RNAs, with the exception of groucho2 RNA, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment correctly. Activation of notch results in ectopic activation of her1 and her4. This misregulation of the expression of her genes might be causally related to the observed mesodermal defects, as her1 and her4 mRNA injections led to effects similar to those seen with notch1a-intra. deltaC and deltaD seem to function after subdivision of the presomitic mesoderm, since the her gene transcription pattern in the presomitic mesoderm remains essentially normal after misexpression of delta genes. Whereas notch signalling alone apparently does not affect myogenesis, zebrafish groucho2 is involved in differentiation of mesodermal derivatives.


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