Transcriptome Analysis Identifies Regulators of Hematopoietic Stem and Progenitor Cells

• HSCs are transcriptionally primed for rapid activation
• A total of 322 HSC-enriched genes, including 51 transcription factors, were identified
• Ectopic Hlf expression increased ex vivo self-renewal in stem and progenitor cells
• Analysis revealed a transcription factor family hypothesized to regulate multipotency

SummaryHematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional units of bone marrow transplantation. To improve the molecular understanding of HSCs and their proximal progenitors, we performed transcriptome analysis within the context of the ImmGen Consortium data set. Gene sets that define steady-state and mobilized HSCs, as well as hematopoietic stem and progenitor cells (HSPCs), were determined. Genes involved in transcriptional regulation, including a group of putative transcriptional repressors, were identified in multipotent progenitors and HSCs. Proximal promoter analyses combined with ImmGen module analysis identified candidate regulators of HSCs. Enforced expression of one predicted regulator, Hlf, in diverse HSPC subsets led to extensive self-renewal activity ex vivo. These analyses reveal unique insights into the mechanisms that control the core properties of HSPCs.