Deciphering the hematopoietic pathway at the single cell level
"Deciphering the hematopoietic pathway at the single cell level: results from cellular barcoding"
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).
More recently, we have shown that the common Myeloid Progenitors (CMP) are made up of distinct subpopulations that either yield erythrocytes or myeloid cells (Perié L et al, submitted). 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. The observation of substantial transcriptional heterogeneity within the CMP pool fits well with this model. Understanding how the interplay between these heterogeneous commitments occurs dynamically in MPPs will be an important future challenge.
Together, these results underscore the value of high-throughput analysis of single cell output in deciphering the hematopoietic pathway.
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