scholarly journals Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling

2015 ◽  
Vol 47 (9) ◽  
pp. 407-419 ◽  
Author(s):  
Elaine M. Richards ◽  
M. Belen Rabaglino ◽  
Andrew Antolic ◽  
Charles E. Wood ◽  
Maureen Keller-Wood

Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor analyses using Webgestalt modeled the biological significances and transcription factors of the gene expression patterns. Modeling indicated a decreased expression of genes associated with anatomical development and differentiation during this period, whereas those associated with increased protein synthesis and growth associated with maturation of the endoplasmic reticulum rose to term but did not further increase from the near term expression. Expression of genes associated with cell responsiveness, for example, immune responses, decreased at term but expression returned by postnatal day 14. Changes in genes related to metabolism showed differential substrate-associated patterns: those related to carbohydrate metabolism rose to term and remained stable thereafter, whereas those associated with fatty acid oxidation facility rose throughout the period. The timing of many of these maturational processes was earlier in relation to birth than in the rodent. The importance of the transcription factors, estrogen-related receptors, and v-myc avian myelocytomatosis viral oncogene homolog was also highlighted in the pattern of gene expression during development of the perinatal sheep heart.

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 15 ◽  
Author(s):  
Zheng Jiang ◽  
Liyong Sun ◽  
Qiang Wei ◽  
Ye Ju ◽  
Xuan Zou ◽  
...  

Magnolia × soulangeana ‘Changchun’ are trees that bloom in spring and summer respectively after flower bud differentiation. Here, we use phenological and morphological observation and RNA-seq technology to study the molecular basis of flowering initiation in ‘Changchun’. During the process of flowering initiation in spring and summer, the growth of expanded flower buds increased significantly, and their shape was obviously enlarged, which indicated that flowering was initiated. A total of 168,120 expressed genes were identified in spring and summer dormant and expanded flower buds, of which 11,687 genes showed significantly differential expression between spring and summer dormant and expanded flower buds. These differentially expressed genes (DEGs) were mainly involved in plant hormone signal transduction, metabolic processes, cellular components, binding, and catalytic activity. Analysis of differential gene expression patterns revealed that gibberellin signaling, and some transcription factors were closely involved in the regulation of spring and summer flowering initiation in ‘Changchun’. A qRT-PCR (quantitative Real Time Polymerase Chain Reaction) analysis showed that BGISEQ-500 sequencing platform could truly reflect gene expression patterns. It also verified that GID1B (GIBBERELLIN INSENSITIVE DWARF1 B), GID1C, SPL8 (SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 8), and GASA (GIBBERELLIC ACID-STIMULATED ARABIDOPSIS) family genes were expressed at high levels, while the expression of SPY (SPINDLY) was low during spring and summer flowering initiation. Meanwhile, the up- and down-regulated expression of, respectively, AGL6 (AGAMOUS-LIKE 6) and DREB3 (DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 3), AG15, and CDF1 (CYCLIC DOF FACTOR 1) might also be involved in the specific regulation of spring and summer flowering initiation. Obviously, flowering initiation is an important stage of the flowering process in woody plants, involving the specific regulation of relevant genes and transcription factors. This study provides a new perspective for the regulation of the flowering process in perennial woody plants.


Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2795-2808 ◽  
Author(s):  
Jomar Patrício Monteiro ◽  
Karl V. Clemons ◽  
Laurence F. Mirels ◽  
John A. Coller ◽  
Thomas D. Wu ◽  
...  

Paracoccidioides brasiliensis is a thermally dimorphic fungus, and causes the most prevalent systemic mycosis in Latin America. Infection is initiated by inhalation of conidia or mycelial fragments by the host, followed by further differentiation into the yeast form. Information regarding gene expression by either form has rarely been addressed with respect to multiple time points of growth in culture. Here, we report on the construction of a genomic DNA microarray, covering approximately 25 % of the genome of the organism, and its utilization in identifying genes and gene expression patterns during growth in vitro. Cloned, amplified inserts from randomly sheared genomic DNA (gDNA) and known control genes were printed onto glass slides to generate a microarray of over 12 000 elements. To examine gene expression, mRNA was extracted and amplified from mycelial or yeast cultures grown in semi-defined medium for 5, 8 and 14 days. Principal components analysis and hierarchical clustering indicated that yeast gene expression profiles differed greatly from those of mycelia, especially at earlier time points, and that mycelial gene expression changed less than gene expression in yeasts over time. Genes upregulated in yeasts were found to encode proteins shown to be involved in methionine/cysteine metabolism, respiratory and metabolic processes (of sugars, amino acids, proteins and lipids), transporters (small peptides, sugars, ions and toxins), regulatory proteins and transcription factors. Mycelial genes involved in processes such as cell division, protein catabolism, nucleotide biosynthesis and toxin and sugar transport showed differential expression. Sequenced clones were compared with Histoplasma capsulatum and Coccidioides posadasii genome sequences to assess potentially common pathways across species, such as sulfur and lipid metabolism, amino acid transporters, transcription factors and genes possibly related to virulence. We also analysed gene expression with time in culture and found that while transposable elements and components of respiratory pathways tended to increase in expression with time, genes encoding ribosomal structural proteins and protein catabolism tended to sharply decrease in expression over time, particularly in yeast. These findings expand our knowledge of the different morphological forms of P. brasiliensis during growth in culture.


2021 ◽  
Vol 22 (18) ◽  
pp. 10054
Author(s):  
Ivan B. Filippenkov ◽  
Vasily V. Stavchansky ◽  
Natalya Yu. Glazova ◽  
Elena A. Sebentsova ◽  
Julia A. Remizova ◽  
...  

Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6–9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1.5 fold change and adjusted p-value (Padj) < 0.05, in samples collected 4.5 h after the ARS. Semax administration produced >1500 DEGs, whereas ACTH(6–9)PGP administration led to <400 DEGs at 4.5 h after ARS. Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions. Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides. Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS. Consequently, the antistress action of MC peptides may be associated with a correction of gene expression patterns that are disrupted during ARS.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3444-3444
Author(s):  
Hong Jiang ◽  
Mary Brigid Bradley ◽  
Carmella van de Ven ◽  
Prakash Satwani ◽  
Laxmi Baxi ◽  
...  

Abstract LPS activates immature DC via TLR4 and induces maturation of DC for initiating antigen presenting activity (Medzhitov; Nat Rev Immunol 2001). We have previously demonstrated decreased gene expression and protein production of IL-12, IL-15, IL-18 in activated CB MNC and decreased DC MLR (Lee/Cairo, Blood 1996; Qian/Cairo, Blood 1997; Wu/Cairo, Blood 100:3668 p51b 2002). Recently, we have identified differential gene expression patterns including differential immunoregulatory and chemokine genes in LPS-CB vs APB Mo by microarray (Jiang/Cairo, J. Immunol 2004). Since the myeloid lineage DC is derived from Mo, we sought to determine in LPS activated CB vs. APB DC, differential expressed genes that associate with TLR4-mediated signaling pathway. Briefly, Mo were purified from fresh CB or APB and cultured for 7 days with GM-CSF & IL-4 [immature DC (iDC)] and LPS [mature DC (mDC)]. Aliquots from iDC and mDC were analyzed for DC immunophenotype, morphology and DC allogeneic antigen activity. mRNA was isolated, reverse transcripted to cDNA, labeled & hybridized to oligonucleotides (Affymetrix, U133A). Data was analyzed by MAS 5.0 (Affymetrix) and GeneSpring 5.0 software (Silicon Genetics). Several genes were analyzed by RT-PCR (One-Step SuperScript, Invitrogen) and protein expression was analyzed by Western Blot (Bio-Rad). Inverted microscopy demonstrated DC mature morphology at day 8 and flow cytometry demonstrated decreased CD14 and increased CD83 expression in CB & APB mDC. We also demonstrated significant increase in the allogeneic stimulatory effects on CD4+ T cells in APB vs. CB mDC. The microarray analysis demonstrated a significant decreased gene expression of TLR4 [3 fold (F)] and CD14 (2.1 F) (p<0.05) in CB vs APB-DC. We further identified LPS significantly induced increased expression of TLR4 downstream signaling molecular genes such as MAPKKK, NF-kB and TANK in APB compared to CB mDC (3–8 F) (p<0.05). There were also significant amplifications of a variety of other gene categories in LPS activated APB vs CB mDC (p<0.05) including cell surface molecule CD80 (3.7F) and IL-2Ra (5.3 F), cytokine IL-23 (3.5F) & IL-12 (13 F), signal transduction STAT1 (3.4F) & IRF-7 (7.7 F), and immunoregulatory TNFSF10 (12F) & ISG20 (39F). Gene expression of NF-kB1, TRAF1 & IRF-7 by RT-PCR demonstrated an increased expression in LPS-APB vs CB mDC and were compatible with microarray. Moreover, Western analysis of IRF-7 demonstrated increased protein expression in LPS-APB vs CB mDC. In summary, we have identified decreased gene expression patterns in LPS-CB vs APB DC, especially those in the TLR4 signal transduction pathway (MAP3K, TRAF, TANK & NF-kB), and suggest these differentially expressed genes may enhance the activation of TLR4 pathway in LPS-APB vs CB DC, resulting in differential regulation of CB vs APB DC antigen presentation capacities. Furthermore, these decreased expressed genes in other molecular categories (e.g.IL-23, IFNg, IL6, CD80, STAT1, IRF-7, SOCS3) in LPS-CB vs APB DC may be partially responsible for differential innate and adaptive immune function of CB vs APB. Moreover, the differential regulated expression of genes may in part help to explain reduced incidence of severe aGVHD, delay in immune reconstitution and/or increased infectious mortality following HLA disparate UCBT.


2003 ◽  
Vol 23 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Akira Sato ◽  
Yuko Matsumoto ◽  
Urara Koide ◽  
Yuki Kataoka ◽  
Nobuaki Yoshida ◽  
...  

ABSTRACT SALL/Sall is a mammalian homolog of the Drosophila region-specific homeotic gene spalt (sal), and heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We earlier reported that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. We have now generated mice lacking Sall2, another Sall family gene. Although Sall2 is expressed mostly in an overlapping fashion versus that of Sall1, Sall2-deficient mice show no apparent abnormal phenotypes. Morphology and gene expression patterns of the mutant kidney were not affected. Mice lacking both Sall1 and Sall2 show kidney phenotypes comparable to those of Sall1 knockout, thereby demonstrating the dispensable roles of Sall2 in embryonic and kidney development.


2010 ◽  
Vol 38 (2) ◽  
pp. 321-326 ◽  
Author(s):  
Jianping Kong ◽  
Douglas B. Stairs ◽  
John P. Lynch

Barrett's oesophagus is the replacement of normal squamous oesophageal epithelium with an intestinalized columnar epithelium. Although some insight has been gained as to what Barrett's oesophagus is, how this columnar epithelium emerges from within a stratified squamous epithelium remains an unanswered question. We have sought to determine whether oesophageal keratinocytes can be trans-differentiated into Barrett's oesophagus cells. Using an Affymetrix microarray, we found unexpectedly that gene-expression patterns in the Barrett's oesophagus were only slightly more similar to the normal small intestine than they were to the normal oesophagus. Thus gene-expression patterns suggest significant molecular similarities remain between Barrett's oesophagus cells and normal squamous oesophageal epithelium, despite their histological resemblance with intestine. We next determined whether directed expression of intestine-specific transcription factors could induce intestinalization of keratinocytes. Retroviral-mediated Cdx2 (Caudal-type homeobox 2) expression in immortalized human oesophageal keratinocytes engineered with human telomerase reverse transcriptase (EPC2-hTERT cells) could be established transiently, but not maintained, and was associated with a reduction in cell proliferation. Co-expression of cyclin D1 rescued proliferation in the Cdx2-expressing cells, but co-expression of dominant-negative p53 did not. Cdx2 expression in the EPC2-hTERT.D1 cells did not induce intestinalization. However, when combined with treatments that induce chromatin remodelling, there was a significant induction of Barrett's oesophagus-associated genes. Studies are ongoing to determine whether other intestinal transcription factors, either alone or in combination, can provoke greater intestinalization of oesophageal keratinocytes. We conclude that, on the basis of gene-expression patterns, Barrett's oesophagus epithelial cells may represent an intermediate between oesophageal keratinocytes and intestinal epithelial cells. Moreover, our findings suggest that it may be possible to induce Barrett's oesophagus epithelial cells from oesophageal keratinocytes by altering the expression of certain critical genes.


2021 ◽  
Author(s):  
Abicumaran Uthamacumaran ◽  
Morgan Craig

Glioblastoma (GBM) is a complex disease that is difficult to treat. Establishing the complex genetic interactions regulating cell fate decisions in GBM can help to shed light on disease aggressivity and improved treatments. Networks and data science offer novel approaches to study gene expression patterns from single-cell datasets, helping to distinguish genes associated with control of differentiation and thus aggressivity. Here, we applied a host of data theoretic techniques, including clustering algorithms, Waddington landscape reconstruction, trajectory inference algorithms, and network approaches, to compare gene expression patterns between pediatric and adult GBM, and those of adult GSCs (glioma-derived stem cells) to identify the key molecular regulators of the complex networks driving GBM/GSC and predict their cell fate dynamics. Using these tools, we identified critical genes and transcription factors coordinating cell state transitions from stem-like to mature GBM phenotypes, including eight transcription factors (OLIG1/2, TAZ, GATA2, FOXG1, SOX6, SATB2, YY1) and four signaling genes (ATL3, MTSS1, EMP1, and TPT1) as clinically targetable novel putative function interactions differentiating pediatric and adult GBMs from adult GSCs. Our study is among the first to provide strong evidence of the applicability of complex systems approaches for reverse-engineering gene networks from patient-derived single-cell datasets and inferring their complex dynamics, bolstering the search for new clinically- relevant targets in GBM.


2021 ◽  
Author(s):  
mackenzie englund ◽  
Sebastian S James ◽  
Riley Bottom ◽  
Kelly Huffman ◽  
Stuart P Wilson ◽  
...  

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. We therefore developed a set of algorithms for quantifying and comparing tissue-wide spatial patterns of gene expression within and across species. Here we apply these algorithms to compare cortex-wide expression of Id2 and RZRβ mRNA in early postnatal mice and voles. We show that neocortical patterns of Id2 expression are moderately conserved between species, but that the degree of conservation varies by cortical layer and area. By comparison, patterns of RZRβ expression are highly conserved in somatosensory areas, and more variable between species in visual and auditory areas. We consider if these differences reflect independent evolution in the 35 million years since the last common ancestor.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Victoria Honnell ◽  
Jackie L. Norrie ◽  
Anand G. Patel ◽  
Cody Ramirez ◽  
Jiakun Zhang ◽  
...  

AbstractSuper-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription factors have complex developmental stage– and cell–type specific expression patterns across the central nervous system. In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Here we show that deletion of one region disrupts retinal progenitor cell proliferation but does not affect cell fate specification. The deletion of another region has no effect on retinal progenitor cell proliferation but instead leads to a complete loss of bipolar neurons. This prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development. Moreover, it provides a unique opportunity to alter expression of individual transcription factors in particular cell types at specific stages of development. This provides a deeper understanding of function that cannot be achieved with traditional knockout mouse approaches.


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