AG Prof. Dr. Albrecht Müller

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Stem cells have been identified in a number of mammalian tissues (e.g. bone marrow, muscle, gut, skin and neural tissues) and they are at the cellular origin of the development and maintenance of many tissues and cell systems. Until recently, it was generally believed that the differentiation potential of a mammalian somatic stem cell is restricted to one tissue only, as in the case of hematopoietic stem cells differentiating into hematopoietic cells. But this basic concept of stem cell biology has been challenged by a series of recent observations that show that stem cells isolated from different mature tissues can give rise to cells of heterologous cell systems (Stem cells plasticity). Thus, mammalian stem cells are apparently capable of fate changes between stem cell systems, although the mechanisms leading to such changes are unclear.


Ruhel Ahmad (GSLS fellow)
Neurogenesis from parthenogenetic human ES cells.

Human parthenogentic embryonic stem cells are important not only for a potential source of human stem cells with improved histocompatibility, but also for future basic studies of epigenetic regulation and developmental/stem cell biology. While parthenogentic ES cells from several species have been successfully used to differentiate into neural and other cell types and are proposed to be used as cell replacement therapies. But the potential of Human parthenogentic embryonic stem cells in cell replacement therapies is unclear. Therefore my research project will be divided into three principal parts:

1. Analysis of the in vitro neural differentiation potential of Human parthenogentic embryonic stem cells phESC (E.S. Revazova et al, 2007)

2. Analysis of brain engraftment following injection of phESC -derived neural progenitors into a murine brain injury model.

3. To determine the imprinting status in phESC cell-derived neural progenitor cells.

Figure: phESCs colonies on human fibroblast.


Soon-Won Choi (GK 1048 fellow)
Analyzing the neural potential of androgenetic murine ESCs

Uniparental (androgenetic, parthenogenetic and gynogenetic) ESCs are interesting cell lines both for basic research and regenerative medicine. Apart from any therapeutic application, however, is the question of whether uniparental ESCs are compromised in their ability to develop into tissue stem cells that are functional and safe after transplantation. To address this issue, we analyzed the neural potential of AG ESCs following blastocyst injection and by stereotactic transplantation into a mouse model of traumatic brain injury. The results show a widespread and balanced distribution of AG donor cells in E12.5 and E16.5 chimeric brains and neural differentiation of AG donor cells in recipient brains after transplantation. In addition, we investigated the imprinting status of AG cells using real-time RT-PCR. The AG ESC-derived neural progenitor cells reveal parent-of-origin-specific expression of imprinted brain genes.

Figure: in vitro and in vivo differentiation of pan-neural progenitor cells (pNPCs) derived from murine ESCs. The co-localization of donor cells (eGFP+) with neural markers (Tuj-1, NeuN and GFAP) were detected by the traumatic brain injury model.

Prof. Dr. Anna-L. Siren, Würzburg

Xiaoli Li (SPP 1356 fellow)
Functional and chromatin analyses of embryonic stem cell pluripotency by reversible knockdown selected chromatin factors

Chromatin modifications play crucial roles during pluripotent embryonic stem cell (ESC) self-renewal and differentiation. For further understanding of the molecular chromatin signatures of pluripotency in mouse ESC, we propose to analyze mechanisms and factors that govern ESC-specific epigenetic patterns. To this end, a panel of selected chromatin factors which are involved in the transcription machinery will be targeted by inducible and reversible RNAi knockdown in mouse ESCs. The resulting loss-of-function phenotypes will be investigated at both the molecular (chromatin patterns) and cellular levels (ESC self-renewal and differentiation). We will analyze global and local chromatin changes and ESC function by a complementary spectrum of state-of-the-art methodology (ChIPchip; intranuclear chromatin modification-specific flow cytometry; chimera analysis following blastocyst injection). The ultimate aim is to identify and further characterize chromatin factors that are necessary for the establishment and maintenance of epigenetic ESC identity.

Strategy used for RNAi knockdown in mouse ESCs ( inducible and reversible Recombinase-mediated-cassette-exchange):


Prof. Dr. Michael Meisterernst,
Dr. Thomas Karl Albert

Institute for Tumor Biology, University Münster,
Robert-Koch-Str. 43, 48149 Münster, Germany

Nadine Obier (GSLS and GK 1048 fellow)
Analysing the loss of pluripotency in early differentiating murine embryonic stem cells

Pluripotent embryonic stem cells (ESCs) have the potential to differentiate into cell types of all 3 germ layers and into germ cells. In vitro differentiation leads to an immediate loss of that potential and to reduced numbers of chimeric animals following blastocyst injection. This indicates that important molecular mechanisms must rearrange the cellular programm within the first hours and days of differentiation. The aim of my project is to characterise these early in vitro differentiating ESCs in terms of their gene expression, epigenetic histone modification and cellular parameters like cell cycle, proliferation and apoptosis. Also, they will be analysed for pluripotency / ES cell status by CFC assay, embryoid body formation assay and by chimera formation following blastocyst injection. The heterogeneous differentiating ESC-cultures will be subfractionated into cell populations with gradually decreasing Oct4-eGFP levels and rescued under ESC-culture conditions. Once a differentiation state that marks the end of pluripotency with irreversible loss of Oct4-eGFP expression is defined, it is planed to manipulate this state by affecting direct interference with histone acetylation and methylation by drug treatment with inhibitors of histone modifying enzymes. It is planed to study whether the end of pluripotency is a strict 'point of no return' or whether there is a 'time window of differentiation commitment and ambiguity' which can be altered into either direction.

Figure: Embryoid body (EB) of OG2 (Oct4-eGFP) mESCs following hanging drop differentitation after 4 days of culture. Particularly the cells located in the outer layers of the EBs have decreased the expression of the pluripotency marker Oct4.


Linda Varagnolo (Erasmus fellow)
Epigenetic characterization of malignant hematopoietic progenitor cells

Epigenetic modifications of DNA and chromatin are crucial players in hematopoietic stem cells development and lineage differentiation. The aim of this study is to characterize global levels of histone methylation in leukemic cell lines with and without mutation of MLL genes. MLL fusion proteins transform hematopoietic precursors to leukemia stem cells. For the study of the epigenetic status of the cell lines the analyses are based on a FACS-methodology that applies staining of intra-nuclear chromatin modifications such as methylated or acetylated histone tails together with cell surface staining. This method allows fast and simultaneous analysis of global levels of chromatin marks in combination with other flow cytometric features such as cell surface staining plus analysis of cell size and granularity. With these analyses we hope to identify characteristic epigenetic patterns that define different types of leukemia taking into consideration the enzymatic activities, like histone H3 Lysine 4 and 79 methylation, as attractive targets for the development of a MLL-directed therapy (Collaboration with Professor Rolf Marschalek).

Figure: Analysis of global H3K4me3 levels. Histogram plot of the H3K4me3 levels in MLL (SEM and RS4,11) and control (KG-1, Reh and MEC-1) cells. FACS data are analyzed with FlowJo FACS data analysis software. The relative mean values are shown (bottom panel).

Prof. Dr. Rolf Marschalek, Frankfurt


Prof. Dr. Albrecht M. Müller
Zinklesweg 10
97078 Würzburg
Phone: +49 (0)931 - 201 45848

Fax: +49 (0)931 - 201 45147

For more information see also:

SPP 1356:
Bayerische Bioethik Kommission:


MSZ Universität Würzburg   
Phone: 0931 - 201-45146 Fax: 0931 - 201-45148  -   Email:

Last update:
17. Mai 2010        -       Copyright MSZ Würzburg 2003