Distinct routes of lineage development reshape the human blood hierarchy across ontogeny
In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34+ cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult ''two-tier'' hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis. Overall design: Using SMARTseq, the expression profile of the new subsets identified in the linked study (12 samples in duplicates) were analyzed using RNA sequencing. The indicated subsets are all derived from neonatal cord blood.
External Link: /pubmed:26541609