A track of the clones: new developments in cellular barcoding

Abstract

International experts from multiple disciplines gathered at Homerton College in Cambridge, UK from September 12-14, 2018 to consider recent advances and emerging opportunities in the clonal tracking of hematopoiesis in one of a series of StemCellMathLab workshops. The group included thirty-five participants with experience in the fields of theoretical and experimental aspects of clonal tracking, and ranged from PhD students to senior professors. Data from a variety of model systems as well as from clinical gene therapy trials were discussed alongside strategies for data analysis and sharing, as well as challenges arising due to underlying assumptions in data interpretation and communication. Recognizing the power of this technology underpinned a group consensus of a need for improved mechanisms for sharing data and analytical protocols to maintain reproducibility and rigor in its application to complex tissues.

Tracking hematopoietic stem cells and their progeny using whole-genome sequencing

“…Studying the behavior of stem cell clones requires a way of tracking them independently of one another. A considerable number of approaches in animal models or in humans undergoing HSC transplantation have been devised, dating back to the use of chromosomal [7] and enzymatic [8] markers to affirm clonal origin [9]. Using irradiation to induce traceable clonal marks, Becker et al [10], Siminovitch et al [11], and Wu et al [12] serially transplanted bone marrow cells from mice and were able to demonstrate formally that the same clonal unit could generate cells of both the myeloid and lymphoid lineages.…”

Clonal tracking of haematopoietic cells: insights and clinical implications

“…Lineage‐tracing has been extensively reviewed elsewhere 1–5 . Fate mapping is a predecessor to lineage tracing and traces the developmental capabilities of a labelled population of cells sharing some characteristic.…”

Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells

“…Moreover, sequence detection limits could also add bias, as it cannot conclusively determine absence of contribution or disappearance of a clone in longitudinal studies. More advanced endogenous barcoding approaches have now been undertaken where HSCs are traced using reporter mice 19 or genetic recombination is used to mark cells in vivo without any additional manipulation 1,19,20 .…”

“…Over the last 5 years, there has been an explosion of new tools to study the biology of large numbers of single cells 1,2 . Functional cell biology techniques have long been used to study single cells, but new molecular techniques have allowed the coupling of cellular and molecular heterogeneity [3][4][5][6] , adding unprecedented resolution to the concepts first investigated using cellular biology techniques.…”