Examining bone marrow sections from the nestin-expressing mice and based on the presence of various molecules on the populations of cells found within, the team identified the nestin-expressing cells as MSCs. These cells, which outnumber the HSCs 10:1, were either in direct contact with the HSCs or in clusters around them.
"This close proximity suggested that there might be some kind of molecular signaling or cross-talk going on that might control HSC maintenance," explains Enikolopov, who has been investigating the consequence of this kind of cell-cell dialogue during tissue and organ development. "One hypothesis is that this interaction directs and regulates growth by teaching different types of cells where they ought to locate themselves and what they should do there."
This seems to be the case, at least in the bone marrow, as the collaborators found that altering the numbers of MSCs has a corresponding effect on the numbers of HSCs. Increasing the numbers of MSCs by injecting mice with a growth hormone caused HSCs to double in number. Inhibiting MSC proliferation via infusions of growth-inhibiting proteins, on the other hand, was followed by a dip in HSC numbers.
The collaborators also explored the consequence of completely eradicating bone marrow MSCs using genetic tools developed in Enikolopov's lab. The CSHL scientists created mice in which only nestin-expressing cellsthe MSCswere programmed to carry a receptor for a toxin molecule. Injecting mice with the toxin thus selectively wiped out the MSCs. As a result, the scientists observed a four-fold reduction in the numbers of HSCs in the bone marrow of these mice. In the absence of bone marrow MSCs, large numbers of HSCs injected into the mice also failed to make their w
|Contact: Hema Bashyam|
Cold Spring Harbor Laboratory