Expression patterns of germ line specific genes in mouse and human pluripotent stem cells are associated with regulation of ground and primed state of pluripotency

Gordeeva, O. F.; Lifantseva, N. V.; Хайдуков, С. В.

doi:10.1134/s1062360411060038

Cited by 7 publications

(10 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our studies of the effects of cytotoxic drugs with different mechanisms of action on the mouse undifferentiated pluripotent cells and teratocarci noma cells showed that their sensitivity to cytostatic drugs used were similar, despite the different origins of cell lines studied. This can be explained by the fact that all lines used had considerably similar structure of the cell cycle (Gordeeva et al, 2011). The time of cyto static exposure was 24 h that significantly longer than population doubling for the ESCs, EGCs and ECCs (14-16 h) and duration of their cell cycle (11-14 h).…”

Section: Discussionmentioning

confidence: 97%

“…Our previous studies have shown that cells of all lines used (R1, EGC 10 and F9) had virtually identical structure of the cell cycle with predominant accumulation of cells in S phase of cell cycle and had similar expres sion profiles of specific genes (Gordeeva et al, 2011). We used the following experimental design: seeding cells in the same density cultivation of undifferen tiated ESCs, EGCs and ECCs until reaching 30-40% confluence exposure to cytostatics for 24 h withdrawal of cytotoxic drugs and cultivation in stan dard medium for the next 24 hours.…”

Section: Toxic and Antiproliferative Effects Of Cytostatic Drugs On Umentioning

confidence: 98%

“…In fact, divided cells enter into a new round of DNA replication almost immediately after the previous mitosis (Savatier et al, 1994(Savatier et al, , 1996Bur 1 The article was translated by the authors. don et al, 2002;Stead et al, 2002;White et al, 2005;Fluckiger et al, 2006;Becker et al, 2006;Gordeeva et al, 2011). In contrast to cancer cells, pluripotent stem cells capable of spontaneous and induced differ entiation.…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Antiproliferative and cytotoxic effects of different type cytostatics on mouse pluripotent stem and teratocarcinoma cells

Gordeeva

2012

Russ J Dev Biol

Self Cite

View full text Add to dashboard Cite

Pluripotent stem cells are able to proliferate indefinitely and differentiate in vitro into various cell types. However, in most cases in vitro differentiation of the pluripotent stem cells is asynchronous and incom plete, and the residual undifferentiated cells can initiate teratoma development after transplantation into recipients. These features of the pluripotent stem cells are the major issue for development of safe cell therapy technologies based on pluripotent stem cells. Considering significant resemblance of growth rates of pluripo tent stem and cancer cells we investigated antiproliferative and cytotoxic effects of different type cytostatics (mitomycin C, etoposide, vinblastine and cycloheximide) on the undifferentiated and differentiating mouse embryonic stem cells, embryonic germ cells, blastocyst and on mouse embryonal teratocarcinoma cells and mouse embryonic fibroblasts. The findings showed that all cytostatics used induced both antiproliferative effects and acute toxic processes in undifferentiated pluripotent stem cells and embryonal teratocarcinoma cells whereas these effects were less in differentiating embryonic stem cells and embryonic fibroblast. More over, the trophoblast cells of mouse blastocysts were less sensitive to damaging effects of cytostatics than inner cell mass cells. The examination of deferred effects of cytostatics revealed that the effects of mitomycin C, etoposide and vinblastine, but not cycloheximide, were irreversible because survived cells were not able to proliferate. Nevertheless, the numbers of embryonic fibroblasts exposed to etoposide or vinblastine remained unchanged while vast majority of undifferentiated pluripotent cells treated underwent apoptosis. Thus, diverse effects of etoposide and vinblastine on the undifferentiated pluripotent stem cells and differentiated embryonic cells allow us to consider these cytostatics and their analogs as drug candidates for selective elim ination of the residual undifferentiated pluripotent stem cells from population of differentiating cells. These findings demonstrate for the first time the possibility of selective elimination of undifferentiated pluripotent stem cells using cytostatic drugs approved for clinic practice. However, to improve effectiveness and safety of this approach and to prevent mutagenic, carcinogenic and teratogenic effects on undifferentiated pluripotent stem cells and their differentiated cell derivatives large scale studies of cytostatic effects using different exper imental design and active doses must be performed.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Toxic and Antiproliferative Effects Of Cytostatic Drugs On Umentioning

confidence: 98%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Antiproliferative and cytotoxic effects of different type cytostatics on mouse pluripotent stem and teratocarcinoma cells

Gordeeva

2012

Russ J Dev Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…DAZL is highly expressed in preimplantation embryos and in all analyzed pluripotent stem cell lines . The presence of DAZL transcripts in early embryos was expected because DAZL is expressed and delivered by the mature oocyte .…”

Section: Role Of Dazl In Embryonic Developmentmentioning

confidence: 96%

The roles of DAZL in RNA biology and development

Smorag

Engel

et al. 2014

WIREs RNA

View full text Add to dashboard Cite

RNA-binding proteins play an important role in the regulation of gene expression by modulating translation and localization of specific messenger RNAs (mRNAs) during early development and gametogenesis. The DAZ (Deleted in Azoospermia) family of proteins, which includes DAZ, DAZL, and BOULE, are germ cell-specific RNA-binding proteins that are implicated in translational regulation of several transcripts. Of particular importance is DAZL, which is present in vertebrates and arose from the duplication of the ancestral BOULE during evolution. Identification of DAZL target mRNAs and characterization of the RNA-binding sequence through in vitro binding assays and crystallographic studies revealed that DAZL binds to GUU triplets in the 3' untranslated region of target mRNAs. Although there is compelling evidence for the role of DAZL in translation stimulation of target mRNAs, recent studies indicate that DAZL can also function in translational repression and transport of specific mRNAs. Furthermore, apart from the well-characterized function of DAZL in gametogenesis, recent data suggest its role in early embryonic development and differentiation of pluripotent stem cells toward functional gametes. In light of the mounting evidence for the role of DAZL in various cellular and developmental processes, we summarize the currently characterized biological functions of DAZL in RNA biology and development.

show abstract

“…However, the self renewal rates and cell culture systems for maintenance of the human embry onic stem cells (hESCs) and mESCs, both derived from blastocysts, are different (Smith et al, 1988;Savatier et al, 1996;Thomson et al, 1998;Burdon et al, 2002;Dahéron et al, 2004;Vallier et al, 2005;Xu et al, 2005;Becker et al, 2006). Moreover, hESCs have been found to be more similar to later embryonic population cultivated in vitro, mouse epiblast stem cells (EpiSCs) in the primed state of pluripotency (Brons et al, 2007;Tesar et al, 2007;Vallier et al, 2009;Hanna et al, 2010;Gordeeva et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Expression of TGFβ family factors and FGF2 in mouse and human embryonic stem cells maintained in different culture systems

et al. 2013

Self Cite

View full text Add to dashboard Cite

Mouse and human embryonic stem cells are in different states of pluripotency (naive/ground and primed states). Mechanisms of signaling regulation in cells with ground and primed states of pluripotency are considerably different. In order to understand the contribution of endogenous and exogenous factors in the maintenance of a metastable state of the cells in different phases of pluripotency, we examined the expression of TGFβ family factors (ActivinA, Nodal, Lefty1, TGFβ1, GDF3, BMP4) and FGF2 initiating the appro priate signaling pathways in mouse and human embryonic stem cells (mESCs, hESCs) and supporting feeder cells. Quantitative real time PCR analysis of gene expression showed that the expression patterns of endoge nous factors studied were considerably different in mESCs and hESCs. The most significant differences were found in the levels of endogenous expression of TGFβ1, BMP4 and ActivinA. The sources of exogenous factors ActivnA, TGFβ1, and FGF2 for hESCs are feeder cells (mouse and human embryonic fibroblasts) expressing high levels of these factors, as well as low levels of BMP4. Thus, our data demonstrated that the in vitro main tenance of metastable state of undifferentiated pluripotent cells is achieved in mESCs and hESCs using dif ferent schemes of the regulations of ActivinA/Nodal/Lefty/Smad2/3 and BMP/Smad1/5/8 endogenous branches of TGFβ signaling. The requirement for exogenous stimulation or inhibition of these signaling pathways is due to different patterns of endogenous expression of TGFβ family factors and FGF2 in the mESCs and hESCs. For the hESCs, enhanced activity of ActivinA/Nodal/Lefty/Smad2/3 signaling by exo genous factor stimulation is necessary to mitigate the effects of BMP/Smad1/5/8 signaling pathways that pro mote cell differentiation into the extraembryonic structures. Significant differences in endogenous FGF2 expression in the cells in the ground and primed states of pluripotency demonstrate diverse involvement of this factor in the regulation of the pluripotent cell self renewal.

show abstract

Expression patterns of germ line specific genes in mouse and human pluripotent stem cells are associated with regulation of ground and primed state of pluripotency

Cited by 7 publications

References 47 publications

Antiproliferative and cytotoxic effects of different type cytostatics on mouse pluripotent stem and teratocarcinoma cells

Antiproliferative and cytotoxic effects of different type cytostatics on mouse pluripotent stem and teratocarcinoma cells

The roles of DAZL in RNA biology and development

Expression of TGFβ family factors and FGF2 in mouse and human embryonic stem cells maintained in different culture systems

Contact Info

Product

Resources

About