Epigenetics Podcast16 Maj 2024

Using Single-Cell Multiomics to Characterize Human Developmental Hematopoiesis (Ana Cvejic)

In this episode of the Epigenetics Podcast, we talked with Ana Cvejic from the Biotech Research & Innovation Centre at the University of Copenhagen about her work on using sc-multiomics to characterise human developmental hematopoiesis.

The conversation starts by delving into Ana's research on hematopoiesis, starting with her work on identifying novel genes controlling blood traits in zebrafish models. She explains her transition to single-cell methodologies and the application of single-cell RNA sequencing to study hematopoietic cells in zebrafish, focusing on thrombocyte lineage commitment and gene expression.

The discussion progresses to her groundbreaking study on human fetal hematopoiesis, where she combined single-cell RNA-seq with single-cell ATAC-seq to understand chromatin accessibility and gene expression dynamics. Ana then shares insights into the identification of new cell surface markers and the priming of hematopoietic stem cells, particularly in conditions like Down syndrome.

Furthermore, she then elaborates on the construction of a phylogenetic tree of blood development using whole-genome sequencing of single-cell-derived hematopoietic colonies from healthy human fetuses. She explains the motivation behind this study, highlighting the insights gained regarding stem cell quantities, developmental timelines, and mutations in blood development.

References

Bielczyk-Maczyńska, E., Serbanovic-Canic, J., Ferreira, L., Soranzo, N., Stemple, D. L., Ouwehand, W. H., & Cvejic, A. (2014). A loss of function screen of identified genome-wide association study Loci reveals new genes controlling hematopoiesis. PLoS genetics, 10(7), e1004450. https://doi.org/10.1371/journal.pgen.1004450
Athanasiadis, E. I., Botthof, J. G., Andres, H., Ferreira, L., Lio, P., & Cvejic, A. (2017). Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis. Nature communications, 8(1), 2045. https://doi.org/10.1038/s41467-017-02305-6
Ranzoni, A. M., Tangherloni, A., Berest, I., Riva, S. G., Myers, B., Strzelecka, P. M., Xu, J., Panada, E., Mohorianu, I., Zaugg, J. B., & Cvejic, A. (2021). Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis. Cell stem cell, 28(3), 472–487.e7. https://doi.org/10.1016/j.stem.2020.11.015

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