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.
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. |
