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The earliest fate split separates erythroid-megakaryocyte progenitors from lymphoid-myeloid progenitors, which separate further into lymphoid, dendritic cell and granulocytic progenitors. Thus, differently from previous works, we also extended our analysis to the whole bone marrow fraction lacking the main markers of terminal differentiation Lin- cells.
In doing so we used a novel graded FACS-sorting strategy that corrects for expansion of cells as they differentiated, and thus allows examining early states alongside later ones that comprise the vast majority of Lin- progenitors. In fractionating the cells by maturity, we made use of a cell surface marker, GeneA, which we identified from the initial data set as capturing cells that are multipotent until just beyond the first branch-point.
The result of this analysis was a high resolution landscape from the transcriptome of 15, single cells, showing multiple branch points, and a topology that remarkably similar to what we reported in mice Tusi et al.
Nature By the in depth analysis of our single-cell maps we generated a number of information of value for the broader hematology community:.
Overall, our study provides a detailed view of the early hematopoietic cell state hierarchy in humans and a valuable resource for HSPC biology. Sign In or Create an Account. Sign In. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function.
Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene. Landscape of transcription in human cells. DOI: UC Irvine. Email Facebook Twitter. Abstract Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells.
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