Whole-transcriptome analysis of endothelial to hematopoietic stem cell transition reveals a requirement for Gpr56 in HSC generation

Parham Solaimani Kartalaei, Tomoko Yamada, Chris Vink, EM (Emma) Pater, Reinier Linden, J Marks-Bluth, Antoine Sloot, Mirjam Van den Hout - van Vroonhoven, T Yokomizo, Lucila Solerno, Ruud Delwel, JE Pimanda, Wilfred van Ijcken, Elaine Dzierzak

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Abstract

Hematopoietic stem cells (HSCs) are generated via a natural transdifferentiation process known as endothelial to hematopoietic cell transition (EHT). Because of small numbers of embryonal arterial cells undergoing EHT and the paucity of markers to enrich for hemogenic endothelial cells (ECs [HECs]), the genetic program driving HSC emergence is largely unknown. Here, we use a highly sensitive RNAseq method to examine the whole transcriptome of small numbers of enriched aortic HSCs, HECs, and ECs. Gpr56, a G-coupled protein receptor, is one of the most highly up-regulated of the 530 differentially expressed genes. Also, highly up-regulated are hematopoietic transcription factors, including the "heptad" complex of factors. We show that Gpr56 (mouse and human) is a target of the heptad complex and is required for hematopoietic cluster formation during EHT. Our results identify the processes and regulators involved in EHT and reveal the surprising requirement for Gpr56 in generating the first HSCs.
Original languageUndefined/Unknown
Pages (from-to)93-106
Number of pages14
JournalJournal of Experimental Medicine
Volume212
Issue number1
DOIs
Publication statusPublished - 2015

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