Abstract
Hematopoietic stem cells (HSCs) possess unique gene expression programs
which enforce their identity and regulate lineage commitment. Long
non-coding RNAs (lncRNAs) have emerged as important regulators of gene
expression and cell fate decisions, although their functions in HSCs are
unclear. Here, we profiled the transcriptome of purified HSCs by deep
sequencing and identified 323 unannotated lncRNAs. Comparing their
expression in differentiated lineages revealed 159 lncRNAs enriched in
HSCs, some of which are likely HSC-specific (LncHSCs). These lncRNA
genes share epigenetic features with protein-coding genes, including
regulated expression via DNA methylation, and knocking down two LncHSCs
revealed distinct effects on HSC self-renewal and lineage commitment. We
mapped the genomic binding sites of one of these candidates and found
enrichment for key hematopoietic transcription factor binding sites,
especially E2A. Together, these results demonstrate that lncRNAs play
important roles in regulating HSCs, providing an additional layer to the
genetic circuitry controlling HSC function.
Text link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388783/
