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Faculty
Ren-He Xu
Associate Professor of Genetics and Developmental Biology
Director, Human Embryonic Stem Cell Facility
renhexu@uchc.edu
Areas of Interest:
The unlimited self-renewal and developmental potential of human
embryonic stem (ES) cells makes them highly promising to produce desired
cells and tissues to treat degenerative diseases. Human ES cells also
represent a unique tool to study the human development given their
direct inheritance from the early human embryo. This new tool is
particularly important because of our limited access to early
post-implantation human embryos and because of the important differences
between human and mouse embryos.
We have previously found that, by treating human ES cells with a TGF-beta
super-family member bone morphogenetic protein 4 (BMP4), the cells
synchronously differentiate into trophoblast, the first differentiated
cell type in mammalian embryos. Trophoblast differentiation is essential
for the formation of the placenta. Recently, we have demonstrated that
basic fibroblast growth factor (bFGF) synergizes with the BMP inhibitor
Noggin to maintain the long-term, undifferentiated proliferation of
human ES cells. This discovery eliminates the need for feeder cells or
feeder-conditioned medium in human ES cell cultures. Interestingly,
other factors that have been reported to promote human ES cell
self-renewal include WNT3a and another group of TGF-beta super-family
members TGF-beta1, ACTIVIN, and NODAL.
My laboratory is interested in understanding the interactions between
the above signaling pathways that govern self-renewal of human ES cells
and their early decisions to differentiate to various cell lineages. We
will also compare the mechanisms of renewal and differentiation between
different human ES cell lines, between human and mouse ES cells, and
between ES cells and embryonal carcinoma cells.
Another important task for me is to direct the human ES cell
facility. It will serve as a core to stock and derive human ES cell
lines and provide expertise on this scientifically and therapeutically
important system to meet the research interests of colleagues throughout
the State of Connecticut.
Lab Rotation Projects:
1. Training in human ES cell culture to help other laboratories that
need the expertise.
2. Expressing transgenes in human ES cells to manipulate the BMP/TGF-beta
signaling pathways.
3. Searching for partner proteins involved in the BMP/TGF-beta signaling
in human ES cells.
4. Identifying target genes of the BMP/TGF-beta signaling and their role
in human ES cells self-renewal and differentiation.
Xu Lab Page
Stem Cell
Core website
Selected Publications:
Levenstein, M.E., Ludwig, T.E., Xu, R.-H., Llanas, R.A., VanDenHeuvel-Kramer,
K., Manning, D., and Thomson, J.A. Basic FGF support of human embryonic
stem cell self-renewal. Stem Cells In press.
Xu, R.-H., Peck, R.M., Li, D.S., Feng, X., Ludwig, T., and Thomson,
J.A. Basic FGF and suppression of BMP signaling sustain undifferentiated
proliferation of human ES cells. Nat Methods 2(3):185-190, 2005.
Specifically commented by Science 307:1393, 2005.
Xu, R.-H. In vitro induction of trophoblast from human embryonic stem
cells. In Michael J. Soares ed. Placental and trophoblast methods and
protocols for Methods in Molecular Medicine Series. Humana Press, Inc.
Totowa, NJ, pp189-202, 2005.
Golos, T. and Xu, R.-H. Trophoblast differentiation from embryonic
stem cells. In Ordorico, J., Pedersen, R., and Zhang, S.-C. ed. Human
embryonic stem cells. BIOS Scientific Publishers Ltd., Oxford, U.K.,
pp101-120, 2005.
Xu, R.-H., Chen, X., Li, D.S., Li, R., Addicks, G.C., Glennon, C.,
Zwaka, T.P., and Thomson, J.A. BMP4 initiates human embryonic stem cell
differentiation to trophoblast. Nat. Biotech. 20(12):1261-4, 2002.
Peng, Y., Xu, R.-H. (equal first author), Mei, J.M., Li, X.-P., Yan,
D.-H., Kung, H.-f., and Phang, J.M. Neural inhibition by c-Jun as a
synergizing factor in BMP-4 signaling. Neurosciece 109(4):657-64, 2002.
Peng, Y., Kok, K.H., Xu, R.-H., Kwok, K.H.H., Fung, P.C.W., Kung,
H.-f., and Lin, M.C.M. Maternal cold inducible RNA binding protein is
required for Xenopus laevis embryonic kidney formation. FEBS Letter.
24130:1-7, 2000.
Xu, R.-H., Peng, Y., Fan, J., Yan, D.-H., Yamagoe, S., Princler, G.,
Sredni, D., Ozato, K., and Kung, H.-f. Histone acetylation is a
checkpoint in FGF-stimulated mesoderm induction. Dev. Dyn. 218:628-635,
2000.
Kim J., Lee, H.-S., Roh, D.-H., Hwang, Y.-S., Xu, R.-H., Kung, H.-f.,
Bae, Y.-C., and Mae-Ja Park. Transcriptional regulation of the
Xbr-1a/Xvent-2 gene by BMP-4 signaling during Xenopus embryonic
development. Korean J. Anatomy 33:595-608, 2000.
Liu, W., Ren, C., Shi, J., Feng, X., He, Z., Xu, L., Lan, K., Xie,
L., Peng, Y., Fan, J., Kung, H.-f., Yao, K.-T., and Xu, R.-H.
Characterization of the functionally related sites in the neural
inducing gene noggin. Biochem. Biophys. Res. Commun. 270:293-297, 2000. |
