Modulation of chromatin modifying factors’ gene expression in embryonic and induced pluripotent stem cells

Luzzani, Carlos; Solari, Claudia; Losino, Noelia; Waisman, Ariel; Romorini, Leonardo; Blüguermann, Carolina; Sevlever, Gustavo; Barañao, Lino; Miriuka, Santiago Gabriel; Guberman, Alejandra

doi:10.1016/j.bbrc.2011.06.070

Cited by 15 publications

(11 citation statements)

References 33 publications

(40 reference statements)

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“…The expression of class I–III members Hdac2 , Hdac6 , and Sirt1 correlates with adult stem cell maintenance, while the expression of class III member Sirt4 associates with differentiation and aging in these stem cells. A recent report from Luzzani et al (2011) examined the transcript levels of HDAC family members in mouse and human ESCs that were in vitro differentiated [29]. The authors found that class I Hdac2 and Hdac3 were differentially regulated in differentiating mouse ESCs (downregulated and upregulated, respectively), and that both class IIa HDAC5 and class IIb HDAC10 were upregulated in differentiating human ESCs [29].…”

Section: Discussionmentioning

confidence: 99%

“…A recent report from Luzzani et al (2011) examined the transcript levels of HDAC family members in mouse and human ESCs that were in vitro differentiated [29]. The authors found that class I Hdac2 and Hdac3 were differentially regulated in differentiating mouse ESCs (downregulated and upregulated, respectively), and that both class IIa HDAC5 and class IIb HDAC10 were upregulated in differentiating human ESCs [29]. We observed a similar down-regulation of Hdac2 in our differentiating mouse SSCs.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells

Kofman

Huszar

Payne

2012

Stem Cell Rev and Rep

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The differentiation of adult stem cells involves extensive chromatin remodeling, mediated in part by the gene products of histone deacetylase (HDAC) family members. While the transcriptional downregulation of HDACs can impede stem cell self-renewal in certain contexts, it may also promote stem cell maintenance under other circumstances. In self-renewing, differentiating, and aging spermatogonial stem cells (SSCs), the gene expression dynamics of HDACs have not yet been characterized. To gain further insight with these studies, we analyzed the transcriptional profiles of six HDAC family members, previously identified to be the most highly expressed in self-renewing SSCs, during stem cell differentiation and aging. Here we discovered that in both differentiating and aging SSCs the expression of Sirt4 increases, while the expression of Hdac2, Hdac6, and Sirt1 decreases. When SSCs are exposed to the lifespan-enhancing drug rapamycin in vivo, the resultant HDAC gene expression patterns are opposite of those seen in the differentiating and aging SSCs, with increased Hdac2, Hdac6, and Sirt1 and decreased Hdac8, Hdac9, and Sirt4. Our findings suggest that HDACs important for stem cell maintenance and oxidative capacity are downregulated as adult stem cells differentiate or age. These results provide important insights into the epigenetic regulation of stem cell differentiation and aging in mammals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells

Kofman

Huszar

Payne

2012

Stem Cell Rev and Rep

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“…The E14-derived Ainv15 and R1 mESC lines were obtained from ATCC and cultured as previously described [ 11 , 12 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

EDA-Containing Fibronectin Increases Proliferation of Embryonic Stem Cells

et al. 2013

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Embryonic stem cells (ESC) need a set of specific factors to be propagated. They can also grow in conditioned medium (CM) derived from a bovine granulosa cell line BGC (BGC-CM), a medium that not only preserves their main features but also increases ESC´s proliferation rate. The mitogenic properties of this medium were previously reported, ascribing this effect to an alternative spliced generated fibronectin isoform that contains the extra domain A (FN EDA+). Here, we investigated if the FN EDA+ isoform increased proliferation of mouse and human ES cells. We analyzed cell proliferation using conditioned media produced by different mouse embryonic fibroblast (MEF) lines genetically engineered to express FN constitutively including or excluding the EDA domain (FN EDA-), and in media supplemented with recombinant peptides containing or not the EDA. We found that the presence of EDA in the medium increased mouse and human ESC’s proliferation rate. Here we showed for the first time that this FN isoform enhances ESC’s proliferation. These findings suggest a possible conserved behavior for regulation of ES cells proliferation by this FN isoform and could contribute to improve their culturing conditions both for research and cell therapy.

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“…Significantly, the crucial male germ cell gene Nanos2 (Suzuki and Saga, 2008) was downregulated in the absence of PGD 2 . Moreover, numerous regulators of pluripotency, such as Sox2 (Takahashi and Yamanaka, 2006), Peg3 (Jiang et al, 2007), Nr2c2 (Wagner and Cooney, 2013), Trim71 (Chang et al, 2012), Lhx1 (Birk et al, 2000), Sall1 (Karantzali et al, 2011), Mtf2 , L1td1 (Narva et al, 2012), Tet1 (Vincent et al, 2013) and Gtf3c3 (Luzzani et al, 2011), were upregulated in the absence of PGD 2 (Table 2; supplementary material Fig. S4A).…”

Section: Germ Cells In Pgd 2 -Depleted Foetal Testes Proliferate Abnomentioning

confidence: 99%

Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis

et al. 2014

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Through intercellular signalling, the somatic compartment of the foetal testis is able to program primordial germ cells to undergo spermatogenesis. Fibroblast growth factor 9 and several members of the transforming growth factor β superfamily are involved in this process in the foetal testis, counteracting the induction of meiosis by retinoic acid and activating germinal mitotic arrest. Here, using in vitro and in vivo approaches, we show that prostaglandin D 2 (PGD 2 ), which is produced through both L-Pgds and H-Pgds enzymatic activities in the somatic and germ cell compartments of the foetal testis, plays a role in mitotic arrest in male germ cells by activating the expression and nuclear localization of the CDK inhibitor p21Cip1 and by repressing pluripotency markers. We show that PGD 2 acts through its Dp2 receptor, at least in part through direct effects in germ cells, and contributes to the proper differentiation of male germ cells through the upregulation of the master gene Nanos2. Our data identify PGD 2 signalling as an early pathway that acts in both paracrine and autocrine manners, and contributes to the differentiation of germ cells in the foetal testis.

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Modulation of chromatin modifying factors’ gene expression in embryonic and induced pluripotent stem cells

Cited by 15 publications

References 33 publications

Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells

Transcriptional Analysis of Histone Deacetylase Family Members Reveal Similarities Between Differentiating and Aging Spermatogonial Stem Cells

EDA-Containing Fibronectin Increases Proliferation of Embryonic Stem Cells

Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis

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