Quantitative Immuno-Hematology

Leïla Perié

The immune system is composed of diverse, functionally distinct cell types that each contributes uniquely to immune responses. During adulthood, these diverse cell types originate from hematopoietic stem cells though a process called hematopoiesis.

Our research interest lies in understanding quantitatively how this diversity is produced and maintained during homeostasis and infection. To tangle this question, we combine experimental and computational approaches of single cell analysis. In particular, we use a lineage tracing method called cellular barcoding that tracks the descendants of individual cells. In addition, our research aims at developing new lineage tracing methodologies to study hematopoiesis not only in mice but also in humans.

Figure 1 : Principle of lentiviral cellular barcoding

Previously, 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 model where hematopoiesis follows a loss of potential mechanism (Perié L et al, Cell Reports, 2014).

Figure 2: Probabilistic models of hematopoiesis
Figure 2: Probabilistic models of hematopoiesis