scholarly journals A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Heidi Hehnly ◽  
David Canton ◽  
Paula Bucko ◽  
Lorene K Langeberg ◽  
Leah Ogier ◽  
...  

Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin−/− mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division.

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.


1962 ◽  
Vol 13 (3) ◽  
pp. 487 ◽  
Author(s):  
CS Sapsford

In the ram, as in other mammals, the sex cords are made up of two types of cell: indifferent cells (derivatives of the coelomic epithelium) and primordial germ cells. In the cords, each type pursues a separate and independent line of development to become respectively the Sertoli cells and the stem cells (type A spermatogonia) of the adult testis. The principal changes taking place in the primordial germ cells (gonocytes) are a reduction in the size and number of the Feulgen-positive particles in the nuclei, the appearance and subsequent fusion of the nucleoli, and, finally, an increase in the size of the nuclei. While these changes are taking place, the cytoplasm increases in volume and inclusions become more numerous. Cells which have undergone all these transformations have been called prospermatogonia. The cells of the germ line are at first more centrally placed in the sex cords than the indifferent cells. Just before spermatogenesis begins, they migrate to the basement membrane of the seminiferous tubules. All germ cells in tubules in which spermatogenesis has been initiated are seen as prospermatogonia. These cells become flattened against the basement membrane, and their nuclei become more oval in shape. They thus become identical with the stem cells of the adult. Little change is evident in the nuclei of the indifferent cells until puberty. Feulgen-positive material is found in the form of coarse granules at earlier stages of development. At puberty, these granules become dispersed to give a much more homogeneous nucleus. Concurrently, nuclei increase in size, and single or double true nucleoli can be identified. During development, increases in cytoplasmic volume take place. Although cell boundaries between indifferent cells cannot be seen in fixed material, phase contrast observations of fresh material have demonstrated that some forms exist as mononucleate units. It could not be determined whether the same was true in the case of Sertoli cells. No striking change in the relative numbers of glandular interstitial cells could be observed at different stages of development.


2015 ◽  
Author(s):  
Heidi Hehnly ◽  
David Canton ◽  
Paula Bucko ◽  
Lorene K Langeberg ◽  
Leah Ogier ◽  
...  

2005 ◽  
Vol 17 (9) ◽  
pp. 67
Author(s):  
J. Hill ◽  
R. Davey ◽  
M. Herrid ◽  
K. Hutton ◽  
B. Kelley ◽  
...  

Male germline cell transfer has produced offspring in mice (Brinster and Zimmermann 1994). Recently the first livestock animal, a goat, was produced (Honaramooz et al. 2003), while early results in cattle are promising (Oatley et al. 2002; Izadyar et al. 2003). There is an opportunity to develop this technology for the beef industry by transferring male germ line stem cells between breeds to improve the genetics of extensive Australian beef herds. This project is a part of the CSIRO National Research Flagship program that combines expertise and facilities in divisions with complementary expertise at Monash University and the University of Sydney. The environmental constraints of Northern Australia dictate that Brahman type animals show far better survival than Bos taurus cattle, although the carcass value of Brahmans is lower than Bos taurus animals. Artificial insemination is impractical in Northern Australia and thus we aim to develop testis cell transfer technique in cattle to permit Brahman bulls to deliver semen from elite Bos taurus or composite bulls, thereby significantly increasing the growth rate, yield and meat quality of the northern beef herd. Experiments using cattle were performed to determine the applicability of techniques used in the mouse. Initial proof of concept has been achieved that germ cell transfer can result in the donor cells successfully colonizing areas of recipient testis. The viability of isolated testis cells following short term (24 h) culture has been demonstrated through transfer into recipient calves. We have completed >50 male germ cell transfers into recipient calves, using ultrasonographic guided injection into the rete testis. Success of this procedure has been demonstrated by persistence of PKH26 dyed donor cells in the seminiferous tubules of a majority of recipients >2 months after transfer. These recipient male calves have not been depleted of their endogenous spermatogonial populations and we thus expect the efficiency of the procedure to increase as depletion procedures (ongoing) are established. Concurrent with these developments has been research into large scale culture of male germ line stem cells to provide large numbers of stem cells for transplant. Culture of testis cell suspensions has demonstrated survival of enriched testis cells under varying media and culture conditions. Initial passaging of testis cell colonies has revealed mixed cell populations (immunohistochemistry positive for spermatogonia and somatic cells). Further studies will aim to demonstrate that these cultured donor cells are able to undergo spermatogenesis in the recipient animals.


2006 ◽  
Author(s):  
Laura K. Braydich-Stolle ◽  
Saber Hussain ◽  
John J. Schlager ◽  
Marie-Claude Hofmann

2013 ◽  
Vol 13 (5) ◽  
pp. 735-750 ◽  
Author(s):  
T. Dittmar ◽  
C. Nagler ◽  
B. Niggemann ◽  
K.S. Zanker

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ameneh Jafari ◽  
Mostafa Rezaei-Tavirani ◽  
Behrouz Farhadihosseinabadi ◽  
Hakimeh Zali ◽  
Hassan Niknejad

AbstractCancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitable reservoir. There are conflicting opinions about the role of human amniotic membrane/fluid mesenchymal stem cells (hAMSCS/hAFMSCs) in cancer, as some studies demonstrating the anticancer effects of these cells and others suggesting their progressive effects on cancer. This review focuses on recent findings about the role of hAMSCs/hAFMSCs in cancer treatment and summarizes the suppressing as well as promoting effects of these cells on cancer progression and underling mechanisms.


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