9 research outputs found
Eupalinilide E Inhibits Erythropoiesis and Promotes the Expansion of Hematopoietic Progenitor Cells
Hematopoietic stem cells (HSCs) are
the progenitor cells that give
rise to all blood cells. The ability to control HSC differentiation
has the potential to improve the success of bone marrow transplants
and the production of functional blood cells <i>ex vivo</i>. Here we performed an unbiased screen using primary human CD34<sup>+</sup> hematopoietic stem and progenitor cells (HSPCs) to identify
natural products that selectively control their differentiation. We
identified a plant-derived natural product, eupalinilide E, that promotes
the <i>ex vivo</i> expansion of HSPCs and hinders the <i>in vitro</i> development of erythrocytes. This activity was
additive with aryl hydrocarbon receptor (AhR) antagonists, which are
also known to expand HSCs and currently in clinical development. These
findings reveal a new activity for eupalinilide E, and suggest that
it may be a useful tool to probe the mechanisms of hematopoiesis and
improve the <i>ex vivo</i> production of progenitors for
therapeutic purposes
Small Molecule Mediated Proliferation of Primary Retinal Pigment Epithelial Cells
Retinal pigment epithelial (RPE)
cells form a monolayer adjacent
to the retina and play a critical role in the visual light cycle.
Degeneration of RPE cells results in retinal disorders such as age-related
macular degeneration. Cell transplant strategies have potential therapeutic
value for such disorders; however, risks associated with an inadequate
supply of donor cells limit their therapeutic success. The identification
of factors that proliferate RPE cells <i>ex vivo</i> could
provide a renewable source of cells for transplantation. Here, we
report that a small molecule (WS3) can reversibly proliferate primary
RPE cells isolated from fetal and adult human donors. Following withdrawal
of WS3, RPE cells differentiate into a functional monolayer, as exhibited
by their expression of mature RPE genes and phagocytosis of photoreceptor
outer segments. Furthermore, chemically expanded RPE cells preserve
vision when transplanted into dystrophic Royal College of Surgeons
(RCS) rats, a well-established model of retinal degeneration
Eupalinilide E Inhibits Erythropoiesis and Promotes the Expansion of Hematopoietic Progenitor Cells
Eupalinilide E Inhibits Erythropoiesis and Promotes the Expansion of Hematopoietic Progenitor Cells
A protein domain-based interactome network for C. elegans early embryogenesis.
Many protein-protein interactions are mediated through independently folding modular domains. Proteome-wide efforts to model protein-protein interaction or "interactome" networks have largely ignored this modular organization of proteins. We developed an experimental strategy to efficiently identify interaction domains and generated a domain-based interactome network for proteins involved in C. elegans early-embryonic cell divisions. Minimal interacting regions were identified for over 200 proteins, providing important information on their domain organization. Furthermore, our approach increased the sensitivity of the two-hybrid system, resulting in a more complete interactome network. This interactome modeling strategy revealed insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.info:eu-repo/semantics/publishe