Connecting cell fate decision networks in hematopoeisis from the outside in

Mol Syst Biol. 6: 418In a developing tissue, a number of cell fate decisions take place: stem cells self‐renew, progenitor cells are born and proliferate or differentiate. We often consider in isolation two sets of factors regulating these cell fate decisions: extracellular influences such as ligands secreted by other cells, and cell‐autonomous, intracellular factors. Cell‐autonomous factors can include specific marker expression levels, or particular gene regulatory programs. Increasingly, these intracellular factors are treated as networks—signal transduction networks and gene regulatory networks. The ligands regulating tissue development also form a network (Frankenstein et al , 2006), connecting cells that secrete them and cells that they target. How these two types of networks, intracellular and extracellular, interact is still mostly unknown. In a pioneering study just published in Molecular Systems Biology, Kirouac et al (2010) connect the dots, identifying specific cytokines as well as some of the crucial intracellular network nodes involved in in vitro hematopoetic stem cell maintenance, expansion, and differentiation.The hematopoietic ‘tissue’ is composed of stem cells (hematopoietic stem cells, HSCs), progenitor cells, and mature cells differentiated into megakaryocytes, monocytes, and erythrocytes. As long as the environment is favorable to their proliferation, stem cells self‐renew and give rise to progenitor cells allowing maintenance or expansion of the tissue. To successfully expand bone marrow or umbilical cord blood in vitro to produce blood cells for clinical applications, the regenerative potential of blood stem cells—their ability to self‐renew—must be maintained in a culture inevitably formed of multiple blood cell …