PLX247160

GSE104689: Maturation of hematopoietic stem cells from pre-hematopoietic stem cells is accompanied by upregulation of programmed death ligand 1

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Hematopoietic stem cells (HSCs) in the fetal liver mature from pre-HSCs that originate in the major arteries of the embryo. To generate HSCs from other cell sources it will be necessary to reproduce the maturation of HSCs from pre-HSCs ex vivo. We refined the markers used to purify pre-HSCs and HSCs matured ex vivo, and compared the transcriptomes of pre-HSCs, ex vivo matured HSCs, and fetal liver HSCs. We found that maturation of pre-HSCs into HSCs in vivo or ex vivo is accompanied by the downregulation of genes involved in embryonic development and vasculogenesis, and upregulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that functional ex vivo-matured and fetal liver HSCs increase the expression of programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on functional HSCs after ex vivo culture. PD-L1 signaling, however, is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for HSC maturation. SOURCE: Long Gao (gaol3@email.chop.edu) - Tan Lab The Children’s Hospital of Philadelphia