Over the past years, clonal tracking has gained the center stage as a unique technology capable
to unveil population dynamics and hierarchical relationships in vivo. We here highlighted the
main open questions related to the in vivo clonal behavior of hematopoietic cells with a particular focus
on hematopoietic stem and progenitor cells and T cells as main targets of cell- and gene-therapies.
We walked through the current methods applied for tracing in vivo dynamics and functions of hematopoietic
cells in animal models and we described the results of early studies conducted on humans.
We specifically focused our attention on the recent use of retroviral/lentiviral vector Integration Site
(IS) analyses to follow stably marked clones and their progeny in vivo. We showed how this molecular
tracking method can be successfully employed in human studies to unveil the clonal behavior of hematopoietic cells, describing
pioneering works conducted on samples from gene therapy treated patients. Clonal tracking through IS identification
still comes with a complex wet-experimental protocol and technical/analytical constraints. In this regard, we reviewed
the features of the available computational tools for the identification and quantification of ISs and we highlighted the potential
future improvements of IS-based tracking, as this technology is becoming a major source of information on in vivo
fate and survival of engineered cells in humans.
Keywords: Clonal tracking, Hematopoietic stem cells, T cells, Integration site analysis.
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