Stowers Institute researchers identify stem cell niche

A research team led by scientists at the Stowers Institute for Medical Research have discovered the location in mice where hematopoietic stem cells (HSCs) reside, often called the HSCs’ microenvironment or “niche.” The team also identified mechanisms involved in controlling the size of the niche and the number of adult HSCs the body produces. This research has solved the puzzle of the hematopoietic stem cell niche first articulated more than 25 years ago and has defined its essential features in both cellular and molecular terms.

The findings are reported in the Oct. 23 issue of Nature.

HSCs are a population of bone marrow cells capable of self-renewal and production of all types of blood cells. Normally these cells cannot function properly outside their exclusive niche. According to Stowers Institute Assistant Investigator Linheng Li, Ph.D., who led the study, the niche not only provides a home for the HSCs but also regulates their numbers. Gaining greater understanding of the stem cell’s niche and its regulatory signals is an important advance toward the goal of using stem cells for therapeutic purposes.

The research team found that a particular subset of osteoblastic cells, called SNO (spindle-shaped N-cadherin-positive osteoblastic) cells, line the surface of trabecular bone in the marrow cavity, support hematopoietic stem cells, and constitute the primary cellular component of the niche where HSCs reside. By interrupting the signaling pathway through the bone morphogenetic protein (BMP) receptor, the team showed that the size of the HSC niche and the number of HSCs could be increased. They concluded that a change in the size of this niche determines the number of stem cells produced, and the BMP signaling pathway controls the niche size and thus the number of stem cells.

“Although we have identified the SNO cells as an important cellular component of the HSC niche, whether SNO cells alone are sufficient to maintain HSCs, particularly in vitro, is not clear at this point,” Dr. Li said. “This merits further investigation.”

Dr. Li’s findings are corroborated in studies undertaken independently by a group of scientists working at the University of Rochester and at Harvard Medical School and published simultaneously in the October 23 issue of Nature.

“Jim and Virginia Stowers believe that highest quality basic research will point the way to more effective means of preventing and curing disease,” said William Neaves, Ph.D., President and CEO of the Stowers Institute. “The work published by Dr. Li and his colleagues in the October 23 issue of Nature typifies the results envisioned by them. His findings open new opportunities for research on the stem cell niche and could eventually lead to more effective methods of restoring stem cells in the bone marrow of cancer patients after radiation and chemotherapy.”

Joining Stowers Institute scientists in conducting the study were researchers from the University of Missouri-Kansas City School of Dentistry and the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. In addition to his primary appointment at the Stowers Institute, Dr. Li holds a faculty appointment at the University of Kansas School of Medicine.

Situated on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts research on the fundamental processes of cellular life. Through basic research of the highest quality, the Stowers Institute seeks insights that will lead to more effective ways of preserving health and preventing disease. The Institute was founded in 1994 by Jim and Virginia Stowers, two cancer survivors who have dedicated their fortune to supporting the basic research that will provide long-term solutions to gene-based diseases.