Activation of Wnt Signaling in Hematopoietic Regeneration

¹ Department of Pharmacology and Cancer Biology, Duke University Medical Center

^* To whom correspondence should be addressed. E-mail: t.reya{at}duke.edu.

	Abstract

Hematopoietic stem cells (HSCs) respond to injury by rapidly proliferating and regenerating the hematopoietic system. Little is known about the intracellular programs that are activated within HSCs during this regenerative process and how this response may be influenced by alterations in signals from the injured microenvironment. Here we have examined the regenerating microenvironment and find that following injury it has an enhanced ability to support HSCs. During this regenerative phase both hematopoietic and stromal cell elements within the bone marrow microenvironment show increased expression of Wnt10b, which we show can function to enhance growth of hematopoietic precursors. Additionally, regenerating HSCs show increased activation of Wnt signaling; this suggests that microenvironmental changes in Wnt expression after injury may be integrated with the responses of the hematopoietic progenitors. Cumulatively, our data reveal that in the hematopoietic system, growth signals are re-activated during tissue injury and provide novel insight into the influence of the microenvironment during injury repair.