scholarly journals Temporally and Spatially Regulated Expression of the Linker Histone H1fx During Mouse Development

2017 ◽  
Vol 65 (9) ◽  
pp. 513-530 ◽  
Author(s):  
Keiko Ichihara-Tanaka ◽  
Kenji Kadomatsu ◽  
Satoshi Kishida

The linker histone H1fx is the least characterized member of the H1 family. To investigate the developmental changes of H1fx, we performed an immunohistochemical analysis of its expression pattern from embryos to adult mice. We found that H1fx was highly expressed during gastrulation, and was positive in all embryonic germ layers between E8.5 and E10.5, which mostly overlapped with the expression of the proliferation marker Ki-67. Neural and mesenchyme tissues strongly expressed H1fx at E10.5. H1fx expression began to be restricted at around E12.5. Western blot analysis of brain tissues demonstrated that the total expression level of H1fx gradually decreased with time from E12.5 to adulthood, whereas H1f0 was increased over this period. In adult mice, H1fx was restrictively expressed at the hypothalamus, subventricular zone, subgranular zone, medulla of the adrenal grand, islets of Langerhans, and myenteric plexus. Taken together, these data suggest that H1fx is preferentially expressed in immature embryonic cells and plays some roles in cells with neural properties.

Author(s):  
Jiao Chen ◽  
Zhonghui Guan

AbstractHuman MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene Mycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.


2021 ◽  
Vol 11 (3) ◽  
pp. 208
Author(s):  
Anna Angelousi ◽  
Georgios Kyriakopoulos ◽  
Fani Athanasouli ◽  
Anastasia Dimitriadi ◽  
Eva Kassi ◽  
...  

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis that needs to be distinguished from adrenocortical adenomas (ACAs). Although, the recently developed transcriptome analysis seems to be a reliable tool for the differential diagnosis of adrenocortical neoplasms, it is not widely available in clinical practice. We aim to evaluate histological and immunohistochemical markers for the distinction of ACCs from ACAs along with assessing their prognostic role. Clinical data were retrospectively analyzed from 37 patients; 24 archived, formalin-fixed, and paraffin-embedded ACC samples underwent histochemical analysis of reticulin and immunohistochemical analysis of p27, p53, Ki-67 markers and were compared with 13 ACA samples. Weiss and Helsinki scores were also considered. Kaplan−Meier and univariate Cox regression methods were implemented to identify prognostic effects. Altered reticulin pattern, Ki-67% labelling index and overexpression of p53 protein were found to be useful histopathological markers for distinguishing ACAs from ACCs. Among the studied markers, only pathological p53 nuclear protein expression was found to reach statistically significant association with poor survival and development of metastases, although in a small series of patients. In conclusion, altered reticulin pattern and p53/Ki-67 expression are useful markers for distinguishing ACCs from ACAs. Immunohistopathology alone cannot discriminate ACCs with different prognosis and it should be combined with morphological criteria and transcriptome analysis.


Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2753-2759 ◽  
Author(s):  
Qiurong Liu ◽  
Fouad Shalaby ◽  
Jamie Jones ◽  
Denis Bouchard ◽  
Daniel J. Dumont

Ship is a recently identified SH2-containing inositol polyphosphate 5-phosphatase that has been implicated as an important signaling molecule in cell-culture systems. To understand the physiologic function of Ship in vivo, we performed expression studies of Ship during mouse development. Results of this study demonstrate the expression of ship to be in late primitive-streak stage embryos (7.5 days postcoitus [dpc]), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in mouse embryo. In adult mice, Ship expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes, and lymphocytes, and is also found in the spermatids of the testis. Furthermore, the level of Ship expression is developmentally regulated during T-cell maturation. These results suggest a possible role for Ship in the differentiation and maintenance of the hematopoietic lineages and in spermatogenesis.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Alduaij ◽  
Katrine Hansen ◽  
Tahreem A. Karim ◽  
Cunxian Zhang ◽  
Michelle M. Lomme ◽  
...  

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.


2018 ◽  
Vol 46 (4) ◽  
pp. 314-322
Author(s):  
V. V. Delektorskaya ◽  
O. N. Solov'eva ◽  
G. Yu. Chemeris ◽  
Yu. I. Patyutko

Background:Well-differentiated pancreatic neuroendocrine tumors (pNETs) represent a group of rare epithelial neoplasms with a highly variable clinical course. AKT1 is one of the most frequently activated protein kinases in pNETs, which promotes the tumor growth and is of interest as a prognostic factor and a target for new treatment approaches.Aim:To study the expression of the phosphorylated variant of AKT1-kinase (p-AKT1) in primary pNETs and their liver metastases and to correlate the results with various clinical and pathological parameters and the disease prognosis.Materials and methods:P-AKT1 expression was studied by the immunohistochemical analysis of the primary lesions and liver metastases in 52 pNETs patients.Results:A high level of cytoplasmic and/or nuclear immunoreactivity was detected in 24/52 of the primary pNETs (46.2%) and in 16/27 of their liver metastases (59.3%). p-AKT1 expression was observed in 3 (21.4%) of NET grade (G) 1, in 14 (46.7%) of NET G2, and in 7 (87.5%) of NET G3. p-AKT1 expression was more frequently identified in pNET G3 category and increased during the tumor progression in metachronous liver metastases, as compared to the corresponding primary tumor. In addition, p-AKT1 positivity was significantly associated with an increase of grade from G1 to G3 (p = 0.004), the Ki-67 index (p = 0.029), the pTNM stage (p = 0.0008), perineural invasion (p = 0.031) and a decrease in disease-free survival (p = 0.05).Conclusion:The results suggest that p-АКТ1 plays an important role in the pathogenesis of pNETs and may be an additional criterion for assessment of the prognosis and treatment effectiveness in this type of tumors.


Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 491-495
Author(s):  
R. Spaventi ◽  
M. Antica ◽  
K. Pavelic

Growth factors have an important role in the regulation of cell growth, division and differentiation. They are also involved in the regulation of embryonic growth and differentiation. Insulin and insulin-like growth factor I (IGF I) play an important part in these events in the later stages of embryogenesis, when organogenesis is completed. In this study, we are presenting evidence that insulin and IGF I are also secreted by embryonic tissues during the prepancreatic stage of mouse development. We found measurable amounts of insulin and IGF I in 8- to 12-day-old mouse embryos. We also showed that embryonic cells derived from 8-, 9- and 10-day-old mouse embryos secrete insulin, IGF I and/or related molecules. Furthermore, the same growth factors, when added to the culture of 9-day-old mouse embryonic cells, stimulate their proliferation. These results lead to the conclusion that insulin can stimulate the growth of embryonic cells during the period when pancreas is not yet formed, which is indirect evidence for a paracrine (or autocrine) type of action.


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