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Kateri A Moore

Publications and source records attributed to Kateri A Moore.

6 recordsLinked to original sources
PubMed2005

A functional genomics approach to hematopoietic stem cell regulation.

Elucidation of the molecular mechanisms that are responsible for regulating the most basic properties of stem cells, self-renewal, and differentiation remains a major challenge in hematopoietic stem cell biology. We have taken a functional genomics approach towards revealing these mechanisms. Previous studies of the fetal liver genetic program led to the development of Stem Cell Database (SCDb, http://stemcell.princeton.edu), a resource for the stem cell community. These studies have been expanded to include the microenvironmental component of hematopoiesis and are the focus herein. In our efforts to study the microenvironmental component we have identified a stromal cell line, AFT024, which serves as a surrogate stem cell niche. The line provides a milieu that facilitates the maintenance of transplantable mouse and human stem cells as well as the generation of large populations of committed progenitors. In a manner mirroring the work done with the SCDb, we provide an online resource, Stromal Cell Database, StroCDB (http://stromalcell.princeton.edu), that is a compendium of information and data derived from biological and molecular studies of this surrogate niche. These include bioinformatic analyses of over 6000 clones derived from a subtracted library enriched for messages expressed in AFT024 as well as data derived from custom expression arrays developed from this library. Herein we describe these efforts and provide a guide for navigating the database and mining the information contained within.

Animals↗
PubMed2004

"Tie-ing" down the hematopoietic niche.

Interaction of hematopoietic stem cells (HSCs) with their particular microenvironment, or niche, is critical for adult hematopoiesis in the bone marrow (BM). Arai et al. (this issue of Cell) demonstrate that HSCs that express the receptor tyrosine kinase Tie2 are quiescent. Ang-1, the ligand for Tie2, enhanced the ability of HSCs to become quiescent and also induced their adhesion to bone, protecting them from stresses that suppress hematopoiesis. These data suggest that the Ang-1/Tie2 signaling pathway plays a crucial role in the maintenance of HSCs in a quiescent state in the BM niche.

Angiopoietin-1↗
PubMed2004

Recent advances in defining the hematopoietic stem cell niche.

PURPOSE OF REVIEW: Hematopoietic stem cells are thought to reside in discrete cellular spaces termed "niches." The cellular elements and matrix surrounding the stem cell within the niche constitute the microenvironment. The purpose of this review is to discuss recent reports that have begun to elucidate the geographic location, key cellular type, and molecular mechanisms operating in stem cell niches. RECENT FINDINGS: Studies that have revealed the osteoblast as the key in vivo cellular element of the adult stem cell niche are the most significant recent findings. Additional studies have highlighted the importance of the Notch and Wingless (Wnt) signaling pathways in the hematopoietic microenvironment. Genomewide expression screens have been used to perform molecular profiling of stromal cell lines that serve as surrogate stem cell niches. These profiles have revealed novel regulatory molecules and have reinforced the roles of classic developmental morphogens in the niche space. The transcriptional profiling from these screens suggests that it is highly unlikely that a single factor or signal transduction pathway will control stem cell properties. SUMMARY: This review highlights the recent advances made toward elucidating the cellular and molecular attributes of the hematopoietic stem cell niche. Complete knowledge of the cellular architecture and molecular mechanisms in stem cell niches is essential to understanding the basic stem cell behaviors of self-renewal and differentiation.

Animals↗
PubMed2002

A stem cell molecular signature.

Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.

Adult↗
PubMed2002

A molecular profile of a hematopoietic stem cell niche.

The hematopoietic microenvironment provides a complex molecular milieu that regulates the self-renewal and differentiation activities of stem cells. We have characterized a stem cell supportive stromal cell line, AFT024, that was derived from murine fetal liver. Highly purified in vivo transplantable mouse stem cells are maintained in AFT024 cultures at input levels, whereas other primitive progenitors are expanded. In addition, human stem cells are very effectively supported by AFT024. We suggest that the AFT024 cell line represents a component of an in vivo stem cell niche. To determine the molecular signals elaborated in this niche, we undertook a functional genomics approach that combines extensive sequence mining of a subtracted cDNA library, high-density array hybridization and in-depth bioinformatic analyses. The data have been assembled into a biological process oriented database, and represent a molecular profile of a candidate stem cell niche.

Amino Acid Sequence↗