Submitted July 22, 2007
Accepted September 30, 2007
Signaling pathways governing stem cell fate
Ulrika Blank, Goran Karlsson, and Stefan Karlsson*
Molecular Med. & Gene Therapy, Inst. of Laboratory Med., & The Lund Strategic Research Center for Stem Cell Biology & Cell Therapy, Lund University Hospital, Lund, Sweden
* Corresponding author; email: stefan.karlsson{at}med.lu.se.
Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem cell biology for several decades. However, paradoxically, while HSCs can be defined by function and even purified to near-homogeneity, the intricate molecular machinery and the signaling mechanisms regulating fate events such as self-renewal and differentiation have remained elusive. Recently, several developmentally conserved signaling pathways have emerged as important control devices of HSC fate, including Notch, Wnt, Sonic hedgehog (Shh) and Smad pathways. HSCs reside in a complex environment in the bone marrow (BM), providing a niche that optimally balances signals that control self-renewal and differentiation. These signaling circuits provide a valuable structure for our understanding of how HSC regulation occurs, concomitantly with providing information of how the BM microenvironment couples and integrates extrinsic with intrinsic HSC fate determinants. It is the focus of this review to highlight some of the most recent developments concerning signaling pathways governing HSC fate.
