Clonal tracking of erythropoiesis in rhesus macaques.

The classical model of hematopoietic hierarchies is being reconsidered on the basis of data from assays and single cell expression profiling. Recent experiments suggested that the erythroid lineage might differentiate directly from multipotent hematopoietic stem cells / progenitors or from a highly biased subpopulation of stem cells, rather than transiting through common myeloid progenitors or megakaryocyte-erythrocyte progenitors. We genetically barcoded autologous rhesus macaque stem and progenitor cells, allowing quantitative tracking of the clonal output of thousands of individual cells over time following transplantation.

Aberrant Clonal Hematopoiesis following Lentiviral Vector Transduction of HSPCs in a Rhesus Macaque.

Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, in contrast to retroviral vectors, are not associated with insertion site-associated malignant clonal expansions and, thus, are considered safer. Here, however, we present a case of markedly abnormal dysplastic clonal hematopoiesis affecting the erythroid, myeloid, and megakaryocytic lineages in a rhesus macaque transplanted with HSPCs that were transduced with a LV containing a strong retroviral murine stem cell virus (MSCV) constitutive promoter-enhancer in the LTR.

Genotoxic Lemons Become Epigenomic Lemonade.

Active regulatory elements in hematopoietic stem cells (HSCs) are incompletely characterized, since extant approaches immunophenotypically define and isolate rare HSCs. In the current issue of Cell Stem Cell, Wünsche et al. (2018) use γ-retroviral insertion sites from a human gene therapy trial to identify the active enhancer landscape of functionally characterized HSCs.