Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity.

Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)-the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate "young-like" HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs.

A comprehensive transcriptome signature of murine hematopoietic stem cell aging.

We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally "young-like" HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively.

The Occurrence of Skeletons of Silicoflagellata and Other Siliceous Bioparticles in Floral Honeys.

Siliceous marine microfossils were unexpectedly discovered during the analysis of flower honey samples from Poland and Tunisia. The microfossils were represented by protist with siliceous skeletons: silicoflagellates, diatoms, and endoskeletal dinoflagellates. This is the first record of such microfossils in honeys. Based on the high percent of anemophilous pollen grains and spores in the sample, it was hypothesized that silicoflagellates were deposited from the air onto the nectariferous flowers, then bees harvested them with the nectar. Based on the comparison of pollen content of honeys and flowering calendar of Tunisia, the harvest time of honey was identified as a period between 1 April and 31 May 2011. Trajectory analysis of air masses in this period confirmed that siliceous microfossils could be aerosolized by wind from the rocks of the so-called Tripoli Formation of Messinian age (6-7 Ma). Similar to the Tunisian case, the Polish trajectory simulation also supports the hypothesis of atmospheric transport of silicoflagellates from outcrops of Oligocene age in the Polish Outer Carpathians. In the case of diatom content of honey, however, the source can be both natural (wind) and artificial (diatomaceous earth filters). For a correct determination, natural sources of siliceous bioparticles, such as wind transport from nearby outcrops should be also considered. Silicoflagellates could be used as complementary indicators of the geographical origin of honeys collected in areas characterized by diatomite outcrops, supporting the results obtained with other methods; thus, such indicators merit further studies within the area of honey authenticity.