Direct lineage reprogramming involves the remarkable conversion of cellular identity. Single-cell technologies aid in deconstructing the considerable heterogeneity that emerges during lineage conversion. However, lineage relationships are typically lost during cell processing, complicating trajectory reconstruction. Here, we present ‘CellTagging’, a combinatorial cell indexing methodology, permitting the parallel capture of clonal history and cell identity, where sequential rounds of cell labelling enable the construction of multi-level lineage trees. CellTagging and longitudinal tracking of fibroblast to induced endoderm progenitor (iEP) reprogramming reveals two distinct trajectories: one leading to successfully reprogrammed cells, and one leading to a ‘dead-end’ state, paths determined in the earliest reprogramming stages. We find that expression of a putative methyltransferase, Mettl7a1, is associated with the successful reprogramming trajectory, where its addition to the reprogramming cocktail increases the yield of iEPs. Together, these results demonstrate the utility of our lineage tracing method to reveal dynamics of direct reprogramming.
Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell–cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40–CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.
The upconversion luminescence ͑UCL͒ of the hexagonal ͑͒-phase NaYF 4 : Yb, Er nanophosphors as a function of temperature ͑300-450 K͒ was examined under 978 nm light excitation. The thermal sensitivity was evaluated based on the UCL intensity ratio between 2 H 11/2-4 I 15/2 and 4 S 3/2-4 I 15/2 transitions ͑R HS ͒. Excitation power, particle sizes ͑37, 65, and 140 nm͒, ion doping concentrations, and with and without silica coating were studied. It was found that R HS is only dependent on temperature at the low excitation power, and has no direct relation with the particle size and surface effects. Silica coating was found to enhance the thermal stability significantly without altering the thermal sensitivity.
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