Figure 2.
Information generated using the WGS approach for studying HSC dynamics. In addition to creating phylogenetic trees using the patterns of shared and unique SNVs generated using the WGS approach, a variety of different types of information can be mined from this type of experiment. For example, the timing of mutation acquisition can be determined for expanded clones. This potentially has significant implications for when and how myeloid cancer–associated mutations should be monitored and when patients should receive therapeutic intervention. Additionally, overall mutation burdens can be estimated and, along with information on mutational signatures, overall clonality, and the range of somatic genetic rescue mutations, these data can help build a more comprehensive picture of the pathways and genes involved in disease-related clonal dynamics. Importantly, the source of cellular material (BM vs PB) was not found to significantly influence these results. Lee-Six et al64 sorted single Lin–CD34+CD38–CD90–CD45RA+ HSCs and bulk HSPCs (megakaryocyte-erythroid progenitors, granulocyte-monocyte progenitors, and common myeloid progenitor) from both PB and BM of the same individual and did not observe any significant differences in mutational burden between the 2 compartments. In addition, the phylogenetic tree built exclusively from 1 source vs the other was not significantly different. This is because the sampled HSCs and HSPCs all report their parent HSCs.

Information generated using the WGS approach for studying HSC dynamics. In addition to creating phylogenetic trees using the patterns of shared and unique SNVs generated using the WGS approach, a variety of different types of information can be mined from this type of experiment. For example, the timing of mutation acquisition can be determined for expanded clones. This potentially has significant implications for when and how myeloid cancer–associated mutations should be monitored and when patients should receive therapeutic intervention. Additionally, overall mutation burdens can be estimated and, along with information on mutational signatures, overall clonality, and the range of somatic genetic rescue mutations, these data can help build a more comprehensive picture of the pathways and genes involved in disease-related clonal dynamics. Importantly, the source of cellular material (BM vs PB) was not found to significantly influence these results. Lee-Six et al64 sorted single LinCD34+CD38CD90CD45RA+ HSCs and bulk HSPCs (megakaryocyte-erythroid progenitors, granulocyte-monocyte progenitors, and common myeloid progenitor) from both PB and BM of the same individual and did not observe any significant differences in mutational burden between the 2 compartments. In addition, the phylogenetic tree built exclusively from 1 source vs the other was not significantly different. This is because the sampled HSCs and HSPCs all report their parent HSCs.

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