Research Synopsis

Stem Cell Niche and Homing

When a stem cell undergoes symmetric or asymmetric division is controlled by its microenvironment or “niche.” Researchers from multiple departments study the role of the niche in stem cell self-renewal. A few of the seminal discoveries regarding the role of the stem cell niche in the control of symmetric vs. asymmetric cell division made by these researchers are highlighted here. Dr. Haifan Lin, the director of the Yale stem cell Center, has made seminal discoveries in the molecular control of the stem cell niche, including identification and characterization of the piwi/ago family genes. His work ranges from Drosophila to mice, and he has continued to be a pioneer in enhancing our understanding of how the niche controls stem cell fate decisions. Dr. Bernard Forget has discovered that the PitX2 transcription factor is expressed on marrow stromal cells that promote hematopoietic stem cell maintenance and self-renewal, and that stromal cells lacking PitX2 do not support hematopoietic stem cell survival/growth. Dr. Weimin Zhong, a leader in the field of regulation of self-renewal versus differentiation down neural pathways during development, has identified that the protein numb as asymmetrically localized when neural stem cells divide asymmetrically. This asymmetric localization of numb leads to daughter cells that have different phenotypes from one another. In her studies on the microenvironment of the adult neural stem cell in the subventricular zone of the rat brain, Dr. Angelique Bordey has shown that GABA regulates whether stem cells undergo self-renewal or remain quiescent. This work has led leaders in the stem cells field to speculate that modulation of GABA signaling could lead to new treatments for brain cancers including neuroendocrine tumors. Dr. Mark Horowitz has exciting data suggesting that, in addition to the endosteal niche, hematopoietic stem and progenitor cells are present within the osteoid (noncalcified bone matrix of bone) and bone itself. In work performed in collaboration with Dr. Diane Krause, they have identified a hematopoietic stem/progenitor cell population that hides out within the bone itself. A better understanding of these cells and their survival within the solid matrix of the bone is ongoing. Dr. Caren Gundberg also works on the microenvironment within the bone marrow. She studies how megakaryocytes promote marrow fibrosis in disease states such as leukemia. Dr. Al Sinusas, an expert in the development of noninvasive imaging approaches for the assessment of myocardial viability, angiogenesis, and post-infarction remodeling. He has been working with Dr. Frank Giordano on tracking labeled marrow derived cells as they home to sites of ischemic injury after myocardial infarction.