Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis.

In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state.

Signaling-to-chromatin pathways in the immune system.

Complex organisms are able to respond to diverse environmental cues by rapidly inducing specific transcriptional programs comprising a few dozen genes among thousands. The highly complex environment within the nucleus-a crowded milieu containing large genomes tightly condensed with histone proteins in the form of chromatin-makes inducible transcription a challenge for the cell, akin to the proverbial needle in a haystack. The different signaling pathways and transcription factors involved in the transmission of information from the cell surface to the nucleus have been readily explored, but not so much the specific mechanisms employed by the cell to ultimately instruct the chromatin changes necessary for a fast and robust transcription activation.

Gene regulatory networks STARR-ing B cells.

A genome-wide screening of functionally active enhancers, combined with analyses of chromatin features, transcription factor binding and gene expression, reveals general principles of gene regulatory networks in activated B cells.