(451e) Studying the Mechanism of Transcriptional Regulation of Mesenchymal Stem Cell Proliferation and Differentiation

Mesenchymal stem
cells (MSCs) are multipotent adult stem cells which can undergo both
self-renewal and multi-lineage differentiation. As an important intracellular
second messenger, cAMP has been shown to induce the differentiation of
mesenchymal stem cells into neural cells. Elevation of cAMP level is usually
tied with the activation of the CREB family proteins, which are important transcription
factors involved in proliferation and differentiation. One target gene of the
CREB family proteins is cyclin D1. This cell cycle regulator is involved in
G1/S phase transition and thus plays a crucial role in proliferation. While
activated CREB induces the transcription of cyclin D1, another member of the
CREB family protein called ICER inhibits the transcription of cyclin D1 by
competing with CREB for binding to the CRE motif. In addition, cyclin D1 has a
kB motif in its promoter region, where the transcription factor NF-kB could bind and induce its transcription.
NF-kB thereby activates the transcription of
cyclin D1 and promotes cell cycle progression. Whether cyclin D1 is
up-regulated or down-regulated largely depends on the relative activity of
CREB, ICER and NF-kB. Since cyclin D1 is
a crucial regulator of G1/S phase transition, its expression may greatly
influence cell cycle progression and consequently affect stem cell
proliferation versus differentiation.