Publication: Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors – University of Copenhagen

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22 March 2016

Publication: Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

Publication

In a new paper, published in Cell, Volume 163, Issue 7, 17 December 2015, Pages 1663–1677, Professor Bo Porse and PhD student Felicia Bratt Lauridsen in a collaborative headed by the group of Ido Amit at the Weizmann Institute in Tel Aviv, have used single-cell transcriptomic analysis to demonstrate an unexpected behavior of myeloid progenitors of the bone marrow.

The hematopoietic system gives rise to all the mature cells of our blood stream and is organized with in a hierarchical manner with the hematopoietic stem and progenitor populations at the apex.

Normally, these populations are defined using surface markers combined with functional assays; however these definitions are not necessarily directly linked with in vivo differentiation potential or gene regulatory mechanisms of these cells.

In this new paper, published in Cell, Volume 163, Issue 7, 17 December 2015, Pages 1663–1677Professor Bo Porse and PhD student Felicia Bratt Lauridsen in a collaborative headed by the group of Ido Amit at the Weizmann Institute in Tel Aviv, have used single-cell transcriptomic analysis to demonstrate an unexpected behavior of myeloid progenitors of the bone marrow. 

Through the use of single-cell RNA-seq the team has generated a comprehensive map of myeloid progenitor subpopulations of the bone marrow. This map uncovers multiple novel progenitor subgroups, unexpected transcriptional priming towards a total of seven differentiation fates and a surprising lack of evidence for progenitors with a mixed state.

Transcriptional priming is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations.

These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution. Moreover these findings challenge current models of hematopoiesis based on progressive loss of differentiation potential.

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Paul, Franziska, Ya’ara Arkin, Amir Giladi, Diego Adhemar Jaitin, Ephraim Kenigsberg, Hadas Keren-Shaul, Deborah Winter, David Lara-Astiaso, Meital Gury, Assaf Weiner, Eyal David, Nadav Cohen, Felicia Kathrine Bratt Lauridsen, Simon Haas, Andreas Schlitzer, Alexander Mildner, Florent Ginhoux, Steffen Jung, Andreas Trumpp, Bo Torben Porse, Amos Tanay & Ido Amit. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors. Cell, doi: 10.1016/j.cell.2015.11.013. (epub ahead of print: November 25, 2015)