Leïla Périé (Institut Curie), Retracing the in vivo haematopoietic tree using single cell lineage tracing methods

Leïla Perié has started in 2015 a junior lab at the Curie Institute in Paris. Her lab is interested in understanding the hematopoietic tree at the single level and combines different experimental and mathematical/computational approaches of lineage tracing to study immune cells and red blood cells production.

Barcoding lineage tracing methods is a powerful experimental technique that simultaneously traces the in vivo differentiation of individual cells. We have showed that individual lymphoid-primed multi-potent progenitors (LMPPs) are generally not multi-outcome; instead, they produce heterogeneous patterns of limited types of blood cells (Naik S, Perié L et al, Nature 2013). Interestingly, contrary to the already known lymphoid and myeloid origin of dendritic cells (DCs), we found that many LMPPs produce several types of DCs without producing any lymphoid and myeloid cells. We then developed a new mathematical framework to infer the nature of the hematopoietic tree and proposed a revised mod (Perié L et al, Cell Reports, 2014).

We have also shown that the common Myeloid Progenitors (CMP) are made up of distinct subpopulations that either yield erythrocytes or myeloid cells (Perié L et al, Cell 2015). Furthermore, based on the labeling of earlier progenitors, we have demontrated that the divergence between the myeloid and erythroid lineage develops within multipotent progenitors (MPP). Collectively, our data provide evidence for a model in which multiple combinations of lineage commitments (e.g. erythroid-myeloid, myelo-lymphoid) occur during the transition of the MPP stage of hematopoietic development.

Together, these results underscore the value of high-throughput analysis of single cell output in deciphering the hematopoietic pathway.