of the Max - MDC

Structure of the Group
Group Leader
Dr. Daniel Besser
Technical Assistant
Françoise André
Graduate Students
Sebastian Diecke
Angel Quiroga-Negreira
Torben Redmer
A
B
Regulation of Pou5F1 and pluripotency genes during early differentiation of hESCs; (A) Immunostaining for Pou5F1 (upper panel), combined with nuclear counterstain
(middle panel) and light microscopy (lower panel) of undifferentiated (undiff.) H9 hESCs or cells differentiated for 1 (1d diff.) or 3 days (3d diff.). Cell
morphology changes significantly after 3 days of differentiation with Pou5F1 protein still detectable. (B) Real-time RT-PCR analysis for the expression of marker
genes for the undifferentiated state, i.e. pou5f1 and nanog, TGFβ signaling, i.e. nodal and lefty-A, and BMP signaling, i.e. msx2 in H9 cells cultured under undifferentiated
conditions (undiff.) and differentiated for different days (1, 3, 5, or 8 days). While the pluripotency genes pou5f1 and nanog drop significantly only
after 5 days of differentiation, nodal and lefty-A levels decrease and msx2 levels increase much earlier, reflecting molecular changes in the cells in the initial
phase of differentiation.
Mesodermal and cardiomyogenic differentiation
in human embryonic and mesenchymal stem cells
(hMSCs)
Torben Redmer, (START-MSC Consortium, BMBF joint
project grant)
A fraction of non-specialized adult stem cells are human
mesenchymal stem cells (hMSCs). They reside in the bone
marrow and adipose tissue but are also present in the cord
blood and may have the potential to become specialized
stem cells, e.g. cardiac progenitor cells. Because it has
already been shown in mice that the VEGF receptor 2
(VEGFR2) is involved in differentiation of cardiac progenitor
cells, we analyzed hMSCs from all three sources by flowcytometry
and real-time RT-PCR for VEGFR2 expression.
Using flow cytometry we observed an expression of the
receptor of nearly 20 % of hMSCs. To study the regulation
of VEGFR2 during early steps of cardiomyogenesis we are
using the formation of embryoid bodies derived from embryonic
stem cell as a model system. Since it is known so far
that the transcription factor MesP1 is crucial for the differentiation
of cardiac progenitor cells coming from the primitive
streak, we are also studying its regulation during
embryoid body formation. We are currently analyzing factors
inducing the expression of MesP1 and VEGFR2 in hMSCs
and are in the process to determine the effects of overexpression
of both proteins.
Selected Publications
James, D, Levine, AJ, Besser, D, and Hemmati-Brivanlou, A.
(2005). TGFβ/activin/nodal signaling is necessary for the
maintenance of pluripotency in human embryonic stem cells.
Development 132, 1273-1282.
Diecke, S, Quiroga-Negreira, A, Redmer, T, and Besser, D.
(2007). FGF2 signaling in mouse embryonic fibroblasts is crucial
for self-renewal of embryonic stem cells. Cells, Tissues Organs, in
press
84 Cancer Research