"Clonal determinants of stem cell heterogeneity"

About:

For decades, biologists have noted that stem-cells in adult tissues show extensive functional heterogeneity. Observations of clonal heritability in hematopoietic stem cell (HSCs) lineage biases have suggested that this heterogeneity is determined by intrinsic and heritable molecules. However, a detailed understanding of the mechanisms driving the variation in tissue stem cell behaviors has remained elusive. We have previously shown that expressed barcodes can enable simultaneous read-out of transcriptome and clonal information from the same single cell. 

We have used these expressed barcodes to carry out dynamic analysis of states and fates for thousands of differentiating clones in parallel and revealed novel regulators of fate decisions. 

Long-term clonal analysis across serial transplantation experiments revealed intrinsic and heritable states driving differences in self-renewal properties. We have recently extended these studies to understand the process of aging and malignancy. Both aged and preleukemic HSCs are characterized by small subsets of clones that expand and self-renew massively with reduced differentiation capacity. In sum, we show that connecting cellular states and cellular fates through high-resolution lineage tracing can be used to describe drivers for a variety of relevant stem cell properties. This could be highly impactful in other in vivo stem cell systems where clonal bottlenecks make conventional functional genomics approaches difficult. 

Bio:

Alejo obtained his PhD in 2014 working in the lab of Fernando Martin-Belmonte on the topics of epithelial morphogenesis and lumen formation at the Centro de Biología Molecular "Severo Ochoa". In 2015, Alejo moved to Boston, MA, to work with Dr. Fernando Camargo (Harvard University) on genetic lineage tracing in development, specializing in single-cell technologies and novel approaches to cellular barcoding. His work as a fellow, uncovering the clonal heterogeneity of hematopoietic stem cells in situ, led to an early independent career in understanding the mechanistic basis for stem cell heterogeneity in homeostasis and disease. 
In 2021, Alejo became a group leader as the head of the Laboratory of Quantitative Stem Cell Dynamics at IRB Barcelona. As a principal investigator, Alejo is focused on developing and applying novel genetic technologies and clonal analysis to understand the molecular mechanisms and physiological consequences of adult stem cell heterogeneity in blood and beyond.

Hosted by PI Clara V. Álvarez.

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