We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists.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 two 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, 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, and deletion of Dnmt3a/b, molecularly resembles HSC rejuvenation or aging, respectively.
Studying fungal diversity in various environmental samples provides us with valuable knowledge about the occurrence of fungi of medical and ecological importance. Moreover, fungal composition may also characterise well the botanical and geographical source of food products, such as the origin of the spore enriched honeydew honeys. Thereby, we identified a wide spectrum of fungi found in 100 of honey samples from various geographical sources -most of them were from Italy, Greece and Hungary. Our honeydew honeys had a higher mean of the number of spore types found in them than floral honeys had. Statistically significant differences in diversity were found regarding the botanical source (p = 1.29 × 10 -9 ) and the climatic classification (p = 2.28 × 10 -2 ) according to KruskalWallis rank sum tests. Most frequently encountered genera included ubiquitous saprotrophic species (Alternaria, Cladosporium, Epicoccum nigrum, Stemphylium), both in floral and honeydew honeys. On the other hand, certain sooty moulds like Aureobasidium pullulans, Tripospermum and Capnobotrys were rather present in different types of honeydew honeys. Metschnikowia reukaufii, the nectar inhabiting yeast reached considerably high quantities in floral honey samples. Present findings encourage further studies on quantifying the occurrence and the indicator value of specific fungal elements in honey, concerning its origin.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.