It might also be possible to make inhibitors that blocked both MRCK isoforms

In contrast, both mitotically quiescent as well as cycling HSC from umbilical cord blood, fetal liver and human fetal bone marrow retained their ability to VE-821 inquirer engraft in NOD/SCID mice. Collectively, these studies established that in adult tissues, a hierarchical order of hematopoietic potential can be assembled based on the mitotic status of HSC whereby only cells in G0 engraft. On the other hand, in the case of prenatal HSC such a hierarchy does not predominate and both cycling and quiescent cells retain their hematopoietic potential. It is therefore possible that genes mediating in vivo stem cell engraftment function may be differentially expressed in adult BM and MPB CD34 + G0 cells, and UCB CD34 + G0 and G1 cells, but not in adult MPB and BM CD34 + cells in G1. Alternatively, one has to consider that if any of the continuum models of stem cell function that have been proposed is operative, then a change in gene expression between cells in G0 versus those in G1, that may control the ability of cells to engraft, should still be detectable even if all cell cycle regulation genes were eliminated from further analysis. The availability of six groups of human CD34 + cells from three distinct tissues with previously established functional capabilities allowed us to carefully investigate the genetic control of pathways implicated in engraftment and to examine the degree of homogeneity or heterogeneity between functionally similar but phenotypically different groups of cells in the absence of the impact of cell cycle regulatory genes. Although microarrays are informative in their ability to measure biological differences at the mRNA level, most functional processes are executed by proteins which become therefore the more relevant parameter for the assessment of operational mechanisms. Recent advances in analyzing global protein expression profiles and in label-free quantification have demonstrated the potential for comparative proteomic studies. Although several studies demonstrated the presence of moderate to poor correlations between microarray and proteomic analyses, implementing both methods may generate complementary and more informative data that cannot be obtained by either method alone. Recently, microarray and proteomic analyses of human and mouse stem cells Enzalutamide in vivo generated insights into the molecular composition of stem cell profiles. In the present study, we investigated the global gene and protein expression profiles of G0 and G1 cells from human BM, MPB, and UCB-derived CD34 + cells by whole genome microarrays and mass spectrometry based proteomic techniques, respectively. Our data provide a unique comparative evaluation of the genomic and proteomic profiles of well-characterized groups of human HSC and illustrate that these analyses may not necessarily generate complementary or compatible results.

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