Search PubMed⌕ Search

Biomedical subjects

Melissa H Wong

Publications and source records attributed to Melissa H Wong.

7 recordsLinked to original sources
PubMed2006

Myeloid lineage progenitors give rise to vascular endothelium.

Despite an important role in vascular development and repair, the origin of endothelial progenitors remains unknown. Accumulating evidence indicates that cells derived from the hematopoietic system participate in angiogenesis. However, the identity and functional role of these cells remain controversial. Here we show that vascular endothelial cells can differentiate from common myeloid progenitors and granulocyte/macrophage progenitors. Endothelial cells derived from transplanted bone marrow-derived myeloid lineage progenitors expressed CD31, von Willebrand factor, and Tie2 but did not express the hematopoietic markers CD45 and F4/80 or the pericyte markers desmin and smooth muscle actin. Lineage tracing analysis in combination with a Tie2-driven Cre/lox reporter system revealed that, in contrast to bone marrow-derived hepatocytes, bone marrow-derived endothelial cells are not the products of cell fusion. The establishment of both hematopoietic and endothelial cell chimerism after parabiosis demonstrates that circulating cells can give rise to vascular endothelium in the absence of acute radiation injury. Our findings indicate that endothelial cells are an intrinsic component of myeloid lineage differentiation and underscore the close functional relationship between the hematopoietic and vascular systems.

Animals↗
PubMed2006

Bone marrow-derived cells fuse with normal and transformed intestinal stem cells.

Transplanted adult bone marrow-derived cells (BMDCs) have been shown to adopt the phenotype and function of several nonhematopoietic cell lineages and promote tumorigenesis. Beyond its cancer enhancing potential, cell fusion has recently emerged as an explanation of how BMDCs regenerate diseased heptocytes, contribute to Purkinje neurons and skeletal and cardiac muscle cells, and participate in skin and heart regeneration. Although bone marrow-derived epithelial cells also have been observed in the intestine, fusion as a mechanism has not been investigated. Here, we show that transplanted BMDCs fuse with both normal and neoplastic intestinal epithelium. Long-term repopulation by donor-derived cells was detected in all principal intestinal epithelial lineages including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, suggesting that the fusion partners of the BMDCs are long-lived intestinal progenitors or stem cells. Fusion of BMDCs with neoplastic epithelium did not result in tumor initiation. Our findings suggest an unexpected role for BMDCs in both regeneration and tumorigenesis of the intestine.

Animals↗
PubMed2005

Epithelial stem cells and their niche: there's no place like home.

Stem cells hold the promise of novel therapy for treating diseases. Unfortunately, the use and study of embryonic stem cells are currently clouded by ethical controversy. Adult stem cells offer a unique alternative in that they may be isolated, studied, or manipulated without harming the donor. Currently, several obstacles for use of adult stem cells as therapy exist. First, the ability to identify most adult stem cells is impeded by lack of stem cell markers. Second, in vitro systems for manipulating adult stem cell populations are often not well defined. Finally, our understanding of how adult stem cells are regulated within their niche is in its infancy. Next to the hematopoietic stem cell, epithelial stem cells are one of the most widely studied stem cell populations. Even so, the diversity between epithelial functions in different organs makes it difficult to determine whether common themes exist in regulating these related stem cells. Although each epithelial stem cell niche possesses unique features to facilitate its specialized functionality, they likely share many common aspects of regulation. The purpose of this review is to compare how the cell signaling influences the stem cell and its niche in rapidly self-renewing epithelia.

Animals↗
PubMed2003

Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells.

During early embryogenesis, blood vessels and hematopoietic cells arise from a common precursor cell, the hemangioblast. Recent studies have identified endothelial progenitor cells in the peripheral blood, and there is accumulating evidence that a subset of these cells is derived from precursors in the bone marrow. Here we show that adult bone marrow-derived, phenotypically defined hematopoietic stem cells (c-kit+, Sca-1+, lineage-) give rise to functional endothelial cells. With the exception of the brain, donor-derived cells are rapidly integrated into blood vessels. Durably engrafted endothelial cells express CD31, produce von Willebrand factor, and take up low-density lipoprotein. Analysis of DNA content indicates that donor-derived endothelial cells are not the products of cell fusion. Self-renewal of stem cells with hematopoietic and endothelial cell potential was revealed by serial transplantation studies. The clonal origin of both hematopoietic and endothelial cell outcomes was established by the transfer of a single cell. These results suggest that adult bone marrow-derived hematopoietic stem cells may serve as a reservoir for endothelial cell progenitors.

Animals↗
PubMed2002

Selection of multipotent stem cells during morphogenesis of small intestinal crypts of Lieberkuhn is perturbed by stimulation of Lef-1/beta-catenin signaling.

Studies of chimeric mice have disclosed that the stem cell hierarchy in the small intestinal epithelium is established during formation of its proliferative units (crypts of Lieberkühn). This process involves a selection among several multipotential progenitors so that ultimately only one survives to supply descendants to the fully formed crypt. In this report, we examine the hypothesis that the level of beta-catenin (beta-cat)-mediated signaling is an important factor regulating this stem cell selection. In the canonical Wnt signaling pathway, beta-catenin can partner with Lef-1/Tcf high mobility group (HMG) box transcription factors to control gene expression. Both Lef-1 and Tcf-4 mRNAs are produced in the fetal mouse small intestine. Tcf-4 expression is sustained, whereas Lef-1 levels fall as crypt formation is completed during the first two postnatal weeks. A Tcf-4 gene knockout is known to block intestinal epithelial proliferation in late fetal life. Therefore, to test the hypothesis, we enhanced beta-catenin signaling in a chimeric mouse model in which the stem cell selection could be monitored. A fusion protein containing the HMG box domain of Lef-1 linked to the trans-activation domain of beta-catenin (Lef-1/beta-cat) was constructed to promote direct stimulation of signaling without being retained in the cytoplasm through interactions with E-cadherin and Apc/Axin. Lef-1/beta-cat was expressed in 129/Sv embryonic stem cell-derived small intestinal epithelial progenitors present in developing B6-ROSA26<-->129/Sv chimeras. Lef-1/beta-cat stimulated expression of a known beta-catenin target (E-cadherin), suppressed expression of Apc and Axin, and induced apoptosis in 129/Sv but not in neighboring B6-ROSA26 epithelial cells. This apoptotic response was not associated with any detectable changes in cell division within the Lef-1/beta-cat-expressing epithelium. By the time crypt development was completed, all 129/Sv epithelial cells were lost. These results indicate that developmental changes in beta-catenin-mediated signaling can play an important role in establishing a stem cell hierarchy during crypt morphogenesis.

Adenomatous Polyposis Coli Protein↗