Stem cells get a grip

Stems cells are regulated by “intrinsic factors” but it’s also becoming increasingly clear that their “stemness” depends on the unique microenvironment called the stem cell niche.

No adult or somatic stem cells have a more complex niche life than hematopoietic stem cells, which give rise to all the different types of blood and immune cells. The bone marrow is their niche. It’s a crowded neighborhood, teeming with different cell types such as fibroblasts, adipocytes, macrophages, and endothelial cells. Hematopoietic stem cells also share their bone marrow niche with osteoblasts, the body’s bone-forming cells, which are derived from a different stem cell population called bone marrow stromal cells. The two stem cells lines probably have a common progenitor but for now scientists can only regard hematopoietic stem cells and osteoblasts as niche neighbors. But it’s a very close relationship, as researchers in the National Institute of Child Health & Human Development laboratory of Jennifer Lippincott-Schwartz now reveal in great detail.

Earlier reports had established that osteoblasts are a crucial component of the hematopoietic stem cell niche and that physical contact with osteoblasts was vital for their survival. The Lippincott-Schwartz lab used live cell imaging techniques to see what happens when the two cell types are put together, directing their attention in particular at the point of cell-cell contact, and how it affects the cellular and molecular relationship of the two cell types.

The NIH researchers observed dynamic amoeboid motility toward the osteoblasts by both human CD34+ hematopoietic progenitor cells and KG1 cells, which are a hematopoietic subset of myeloid progenitors. The progenitor cells assumed a polarized morphology with a leading edge structure and a foot-like “special domain” projection from the cell’s trailing edge called a uropod. It was through this foot that the hematopoietic stem cells took hold of the osteoblasts. The uropod contact point was enriched in the cholera toxin B subunit, a lipid raft molecule, as well as the stem cell marker CD133.

The researchers had seeded the outside of the progenitor cells with microscopic markers, quantum dot nanocrystals, and watched as the dots were taken into the cells and delivered specifically to the uropod domain at the point of contact. Interestingly, time-lapse microscopy detected transfer of the quantum dots from the progenitor cells to the osteoblastic cells, suggesting an intercellular transfer of cell-associated molecules. Immune cells are known to transfer cell-surface molecules during cell-cell interactions so a similar intercellular transfer between hematopoietic progenitors and osteoblasts could be of broad biological significance, the researchers say. Further studies will explore how these close neighbors pull together in the hematopoietic niche.