Biomedical Engineering Reference
In-Depth Information
roles ranging from embryonic development and organogenesis (fetal stem cells
including embryonic stem cells) to tissue homeostasis and regeneration (adult stem
cells). Stem cell development is a complex process: a precise balance is maintained
among different cell events including self-renewal, differentiation, apoptosis (cell
death), and migration. Loss of this balance tends to lead to uncontrolled cell growth/
death, thereby developing into a variety of diseases including tissue defects or can-
cer. To investigate the molecular mechanisms that control stem cell properties we
use the combined approaches described as follows:
•
A global view of the changes in the gene expression patterns during hematopoietic
stem cell development to reveal important pathways regulating hematopoietic
stem cell self-renewal and lineage commitment. The Notch, Wnt, and BMP sig-
nal pathways have been well documented to be involved in cell fate determina-
tion during embryogenesis [
11-
14
] . Expression of Notch, BMP4, and beta-Catenin
(a transcription factor) in hematopoietic stem cells suggests that these pathways
may play important roles in the regulation of hematopoietic stem cell prolifera-
tion and differentiation [
3
] .
To further characterize the functions of these pathways, we use genetic approaches
•
such as transgenic or gene targeting animal models to examine their influence on
stem cell development. Our goal is to understand how these signal pathways or
mechanisms regulate normal development in the hematopoietic system. This
information should reveal how they may malfunction or be altered in association
with human diseases, such as leukemias, lymphomas, or autoimmune diseases.
References
1. Li L, Xie T (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol
17:605-631
2. He XC, Zhang J, Li L (2005) Cellular and molecular regulation of hematopoietic and intestinal
stem cell behavior. In: Stem cell biology: development and plasticity, vol 1049. Annals of the
New York Academy of Sciences, New York, pp 28-38
3. Zhang J, Li L (2005) BMP signaling and stem cell regulation. Dev Biol 284:1-11
4. Li L (2005) Find the hematopoietic stem cell niche in placenta. Dev Cell 8:297-304
5. Tian Q, Feetham MC, Tao WA, He XC, Li L, Aebersold R, Hood L (2004) Proteomic analysis
identifies that 14-3-3{zeta} interacts with {beta}-catenin and facilitates its activation by Akt.
Proc Natl Acad Sci USA 101(43):15370-15375
6. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann
LM, Mishina Y, Li L (2004) BMP signaling inhibits intestinal stem cell self-renewal through
suppression of Wnt-beta-atenin signaling. Nat Genet 36:1117-1121
7. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harri
S, Wiedemann LM, Mishina Y, Li L (2003) Identification of the haematopoietic stem cell niche
and control of the niche size. Nature 425:836-841
8. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J, Li L (2003)
Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierar-
chically controlled during early hematopoiesis. Blood 101(2):383-389
