TY - JOUR
T1 - Whole-transcriptome analysis of endothelial to hematopoietic stem cell transition reveals a requirement for Gpr56 in HSC generation
AU - Kartalaei, Parham Solaimani
AU - Yamada-Inagawa, Tomoko
AU - Vink, Chris S.
AU - de Pater, Emma
AU - van der Linden, Reinier
AU - Marks-Bluth, Jonathon
AU - van der Sloot, Anthon
AU - van den Hout, Mirjam
AU - Yokomizo, Tomomasa
AU - More Authors, null
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84921418392&partnerID=8YFLogxK
U2 - 10.1084/jem.20140767
DO - 10.1084/jem.20140767
M3 - Article
C2 - 25547674
AN - SCOPUS:84921418392
SN - 0022-1007
VL - 212
SP - 93
EP - 106
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -