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New tool reveals insights into maturation of red blood cells

Using detailed genetic data along with a recently developed analytical tool called “population balance analysis” (PBA), investigators have developed models capable of predicting the mature blood cell type of early stage (progenitor) blood cells. Scientists have grappled with how to design studies that will reveal what controls or drives progenitor cells to undergo a process that ultimately leads to becoming more specialized mature cells (e.g., red blood cells). With previous significant technological advances, scientists are now able to use an approach called single-cell expression profiling to begin to understand what cell and tissue types will arise from an individual progenitor cell. In single-cell expression profiling, the “transcriptome” is characterized to provide a measure of a single cell’s gene activity. Active genes produce transcripts, which may serve as instructions for making proteins. A transcriptome is a collection of all the transcripts present in a given cell and gives an internal snapshot of what the cell is doing or how it is changing.

Using the transcriptome data of 4,763 individual cells, researchers showed that progenitor cells from female mice mature along distinct branches leading to one of seven blood cell fates. To understand pathways that progenitor cells might follow as they mature, the investigators had previously developed the analytical tool, PBA, to predict cell fate likelihood using snapshots of single-cell transcriptomes. PBA identified the commitment likelihood for each blood progenitor cell to each of the seven blood cell fates, and these predictions were confirmed by tracking the cell fate process. Unlike the classical models of blood cell maturation, the details provided by PBA revealed that the process is a continuous progression (rather than discrete stages of cell development). For example, the researchers were able to map the continuity of the red blood cell maturation process, called erythropoiesis, from the earliest progenitor cell to the final maturation stage. During these experiments, the researchers uncovered new insights in red blood cell development, including the first identification of IL-17A, a growth factor, as a strong stimulator of red blood cell maturation. The new knowledge obtained from single-cell data combined with PBA has allowed an in-depth examination of early stage blood cell maturation. This approach may provide similar insights into other cell maturation processes, and provides tools to further the fields of stem cell biology and regenerative medicine.

References

Tusi BK, Wolock SL, Weinreb C,…Socolovsky M. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature 555: 54-60, doi: 10.1038/nature25741, 2018.
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