Biomedical subjects

Daniel A Anderson

Publications and source records attributed to Daniel A Anderson.

3 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↗

PubMed2005

Donor marker infidelity in transgenic hematopoietic stem cells.

Transgenic marking approaches are increasingly used to evaluate the developmental potential of stem cells. However, cell fate mapping studies using different transgenic marking systems have produced conflicting results. These disparate findings may be due in part to the infidelity of donor marker gene expression. Analysis of hematopoietic stem cells (c-Kit+, Sca-1+, lineage marker- [KSL]) from a transgenic mouse (1Osb) engineered to ubiquitously express the enhanced green fluorescent protein (EGFP) reveals two distinct populations. Forty percent of KSL cells demonstrate intermediate levels of EGFP fluorescence and differentiate into subpopulations of B cells, T cells, and myeloid cells that do not express EGFP. By contrast, progeny of the remaining 60% of KSL cells are almost exclusively EGFP bright. Long-term multilineage hematopoietic reconstitution and serial transplantation experiments show that these differences in EGFP are a property of self-renewing stem cells. Furthermore, both the transgene integration site and the activation status of a cell are important determinants of EGFP expression. These results indicate that a combination of donor cell markers is required to reliably track the full differentiation potential of transgenic stem cells.

Animals↗

PubMed2004

Transplanted human bone marrow contributes to vascular endothelium.

Recent evidence indicates that bone marrow is a source of endothelial progenitor cells that are mobilized into the peripheral blood in response to cytokines or tissue injury. Previously, we showed that functional endothelial cells (ECs) can be clonally derived from phenotypically defined hematopoietic stem cells. To determine the EC potential of human bone marrow and peripheral blood stem cells, blood vessels in sex-mismatched transplant recipients were evaluated. EC outcomes were identified by using a combination of immunohistochemistry and XY interphase FISH. Donor-derived ECs were detected in the skin and gut of transplant recipients with a mean frequency of 2% and could readily be distinguished from CD45-expressing hematopoietic stem cells. None of the >4,000 ECs examined had more than two sex chromosomes, consistent with an absence of cell fusion. Y chromosome signals were not detected in sex-matched female recipients, excluding the vertical transmission of male cells. None of the recipients evaluated before hematopoietic engraftment demonstrated donor-derived ECs, indicating a close linkage between the recovery of hematopoiesis and EC outcomes. Transplantable bone marrow-derived endothelial progenitor cells may represent novel therapeutic targets for hematopoietic and vascular disease.

Biopsy↗