Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages

Abstract

To elucidate the transcriptional landscape that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitors spanning the earliest stages of B and T lymphoid specification. Over 3000 novel long non-coding RNA genes (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage-specific and more lineage-specific than protein coding patterns. Protein-coding genes co-expressed with neighboring lncRNA genes were enriched for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships between the earliest progenitors in the human bone marrow and thymus.

Long noncoding RNAs in B-cell development and activation

“…Translating genome-scale lncRNA identification into in vivo functional studies remains a major challenge that necessitates the use of model organisms. Previous work has identified lncRNAs expressed in a subset of these populations in humans 17,[33][34][35] ; however, given the high tissue specificity and rapid evolution of lncRNAs, a murine catalog is therefore a prerequisite to successful lncRNA studies in the mouse. In addition, we defined patterns of expression, chromatin modification, and transcription factor binding that provide insight into the regulation and function of these transcripts and we identified a subset of lncRNAs that have human orthologs and thus are of direct relevance to human research.…”

“…Taking advantage of the fact that eRNAs are a distinct class of lncRNA throughout B-cell development (supplemental Figure 6D), we compared mouse eRNAs with human eRNAs reported in CD19 1 B cells. 34 Pairing eRNAs adjacent to orthologous human and mouse coding genes identified a further 228 mouse eRNAs that have 1 or more human eRNA counterparts (supplemental Table 6). Such conserved location indicates that the human/mouse pairs may be marking enhancers of orthologous coding genes.…”

“…17,[33][34][35] Based on pairwise genomic alignments, we identified 185 mouse lncRNAs that have a human syntenic ortholog (supplemental Table 6). Taking advantage of the fact that eRNAs are a distinct class of lncRNA throughout B-cell development (supplemental Figure 6D), we compared mouse eRNAs with human eRNAs reported in CD19 1 B cells.…”

Acute Thymic Involution and Mechanisms for Recovery

“…lncRNAs play a key role in the initial stages of postnatal lymphopoiesis and lymphoid commitment in the human thymus and bone marrow (Casero et al 2015). Modulated expression of lncRNAs under LPS-induced stress has been identified in human monocytes, and these molecules are therefore considered to be essential regulators of the innate immune response (Ilott et al 2014).…”

The significance of low levels of LINC RP1130-1 expression in human hepatocellular carcinoma

“…lncRNA is not as well characterized as other small non-coding RNA such as microRNA, but lncRNAs play important roles in the regulation of a variety of cellular processes, including stem cell pluripotency, cell growth, cell proliferation, apoptosis, metabolism, and cancer cell migration (16)(17)(18)(19)(20)(21). Functional lncRNA may be useful in cancer diagnosis and evaluation of prognosis and it may serve as a potential therapeutic target.…”