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Articles by W. Engel
Total Records ( 3 ) for W. Engel
  U Zechner , J Nolte , M Wolf , K Shirneshan , N. E Hajj , D Weise , B Kaltwasser , A Zovoilis , T Haaf and W. Engel
 

Recently, several groups described the isolation of mouse spermatogonial stem cells (SSCs) and their potential to develop to embryonic stem cell (ESC)-like cells, so-called multipotent germline stem cells (mGSCs). We were the first to derive such mGSCs from SSCs isolated from adult mouse testis and, therefore, called these mGSCs multipotent adult germline stem cells (maGSCs). Here, we comparatively analyzed gene-specific and global DNA methylation profiles as well as the telomerase biology of several maGSC and male ESC lines. We show that undifferentiated maGSCs are very similar to undifferentiated male ESCs with regard to global DNA methylation, methylation of pluripotency marker gene loci, telomerase activity and telomere length. Imprinted gene methylation levels were generally lower in undifferentiated maGSCs than in undifferentiated male ESCs, but, compared with undifferentiated mGSCs derived by other groups, more similar to those of male ESCs. Differentiation of maGSCs increased the methylation of three of the four analyzed imprinted genes to almost somatic methylation patterns, but dramatically decreased global DNA methylation. Our findings further substantiate the pluripotency of maGSCs and their potential for regenerative medicine.

  A Zovoilis , A Pantazi , L Smorag , L Opitz , G. S Riester , M Wolf , U Zechner , A Holubowska , C. L Stewart and W. Engel
 

Cells originating from the germ cell lineage retain the remarkable property under special culture conditions to give rise to cells with embryonic stem cell (ESC) properties, such as the multipotent adult germline stem cells (maGSCs) derived from adult mouse testis. To get an insight into the mechanisms that control pluripotency and differentiation in these cells, we studied how differences observed during in vitro differentiation between ESCs and maGSCs are associated with differences at the level of microRNAs (miRNAs). In this work, we provide for a first time a connection between germ cell origin of maGSCs and their specific miRNA expression profile. We found that maGSCs express higher levels of germ cell markers characteristic for primordial germ cells (PGCs) and spermatogonia compared with ESCs. Retained expression of miR-290 cluster has been previously reported in maGSCs during differentiation and it was associated with higher Oct-4 levels. Here, we show that this property is also shared by another pluripotent cell line originating from the germ line, the embryonic germ cells. In addition, we provide proof that the specific miRNA expression profile of maGSCs has an impact on their differentiation potential. Low levels of miR-302 in maGSCs during the first 10 days of leukaemia inhibitory factor deprivation are shown to be necessary for the maintenance of high levels of early germ cell markers.

  S Meyer , J Nolte , L Opitz , G Salinas Riester and W. Engel
 

DNA microarray analysis was performed with mouse multipotent adult germline stem cells (maGSCs) and embryonic stem cells (ESCs) from different genetic backgrounds cultured under standard ESC-culture conditions and under differentiation-promoting conditions by the withdrawal of the leukemia inhibitory factor (LIF) and treatment with retinoic acid (RA). The analyzed undifferentiated cell lines are very similar based on their global gene expression pattern and show 97–99% identity dependent on the analyzed background. Only 621 genes are differentially expressed in cells derived from mouse 129SV-background and 72 genes show differences in expression in cells generated from transgenic Stra8-EGFP/Rosa26-LacZ-background. Both maGSCs and ESCs express the same genes involved in the regulation of pluripotency and even show no differences in the expression level of these genes. When comparing maGSCs with previously published signature genes of other pluripotent cell lines, we found that maGSCs shared a very similar gene expression pattern with embryonic germ cells (EGCs). Also after differentiation of maGSCs and ESCs the transcriptomes of the cell lines are nearly identical which suggests that both cell types differentiate spontaneously in a very similar way. This is the first study, at transcriptome level, to compare ESCs and a pluripotent cell line derived from an adult organism (maGSCs).

 
 
 
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