Project description:Hematopoietic stem cells (HSCs) possess unique gene expression programs that 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.
Project description:Long non-coding RNAs (lncRNAs) have recently emerged as new players in gene expression regulation. Whether and how lncRNAs might control hematopoietic stem cell (HSC) function remains largely unknown. Here, we profiled the transcriptome of purified long-term HSCs by deep RNA-sequencing and identified thousands of un-annotated transcripts of which 323 are predicted to be lncRNAs. Comparison of their expression in differentiated lineages represented by B cells (B220+) and Granulocytes (Gr1+), revealed that 159 are likely to be HSC-specific. Knockdown of two such non-coding genes (LincHSC-1 and LincHSC-2) indicated that they regulate HSC lineage differentiation, possibly via targeting cell cycle regulators and chromatin modification enzymes. Taken together, we comprehensively identify lncRNAs in HSC and show to examples that play important roles in HSC function.
Project description:Long non-coding RNAs (lncRNAs) have recently emerged as new players in gene expression regulation. Whether and how lncRNAs might control hematopoietic stem cell (HSC) function remains largely unknown. Here, we profiled the transcriptome of purified long-term HSCs by deep RNA-sequencing and identified thousands of un-annotated transcripts of which 323 are predicted to be lncRNAs. Comparison of their expression in differentiated lineages represented by B cells (B220+) and Granulocytes (Gr1+), revealed that 159 are likely to be HSC-specific. Knockdown of two such non-coding genes (LincHSC-1 and LincHSC-2) indicated that they regulate HSC lineage differentiation, possibly via targeting cell cycle regulators and chromatin modification enzymes. Taken together, we comprehensively identify lncRNAs in HSC and show to examples that play important roles in HSC function.
Project description:Long non-coding RNAs (lncRNAs) have recently emerged as new players in gene expression regulation. Whether and how lncRNAs might control hematopoietic stem cell (HSC) function remains largely unknown. Here, we profiled the transcriptome of purified long-term HSCs by deep RNA-sequencing and identified thousands of un-annotated transcripts of which 323 are predicted to be lncRNAs. Comparison of their expression in differentiated lineages represented by B cells (B220+) and Granulocytes (Gr1+), revealed that 159 are likely to be HSC-specific. Knockdown of two such non-coding genes (LncHSC-2 and LncHSC-1) indicated that they regulate HSC lineage differentiation, possibly via targeting cell cycle regulators and chromatin modification enzymes. Taken together, we comprehensively identify lncRNAs in HSC and show to examples that play important roles in HSC function.
Project description:Genomic analyses estimated that the proportion of the genome encoding proteins corresponds to approximately 1.5%, while at least 66% are transcribed, suggesting that many non-coding DNA-regions generate non-coding RNAs (ncRNAs). The relevance of these ncRNAs in biological, physiological as well as in pathological processes increased over the last two decades with the understanding of their implication in complex regulatory networks. This review particularly focuses on the involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of hematopoiesis. To date, miRNAs have been widely studied, leading to a wealth of data about processing, regulation and mechanisms of action and more specifically, their involvement in hematopoietic differentiation. Notably, the interaction of miRNAs with the regulatory network of transcription factors is well documented whereas roles, regulation and mechanisms of lncRNAs remain largely unexplored in hematopoiesis; this review gathers current data about lncRNAs as well as both potential and confirmed roles in normal and pathological hematopoiesis.