Figure 2.
Regulation of mammalian cell differentiation by lncRNAs. Examples are shown of lncRNAs implicated in modulating the differentiation of specialized cells from their progenitors. (A) Many lncRNAs are required for maintenance of the pluripotent state of ES cells, thereby antagonizing differentiation into specialized lineages [10,11,98]. Others favour differentiation [57], and yet others contribute to dedifferentiation of specialized cells into iPS cells [75]. (B) Other lncRNAs are important for the maintenance of adult epidermal lineage progenitor cells [76,77]. (C) Several lncRNAs transcribed from Hox clusters regulate the transcription of Hox genes in cis [57,58,87] or in trans [56], contributing to the distinct epigenetic profiles of Hox loci across cells from distinct anatomical positions. [82,83,84,87]. (D) lncRNAs have also been associated with the development of cells from haematopoietic [50,86,87] and vascular endothelial lineages (E; [88]). (F) Differentiation of muscle cells is also regulated by lncRNAs [65]. (G) Many lncRNAs are differentially expressed and specifically localized across neural tissues during development and disease. Many of them modulate differentiation of progenitors into excitatory, inhibitory or retinal photoreceptor neurons, whereas others favour oligodendrocyte differentiation [93,94,95,96,97,98]. ANCR, anti-differentiation ncRNA; EGO, eosinophil granule ontogeny; ES, embryonic stem; Evf2, embryonic ventral forebrain 2; HOTAIR, HOX antisense intergenic RNA; HOTAIRM1, HOX antisense intergenic RNA myeloid 1; HOTTIP, HOXA transcript at the distal tip; Hox, homeobox; iPS, induced pluripotent stem; linc-MD1, linc muscle differentiation 1; lincRNA-EPS, lincRNA erythroid pro-survival; lincRNA-ROR, lincRNA regulator of reprogramming; lncRNA, long non-coding RNA; Nkx2.2as, natural killer cell-associated antigen 2 locus 2 antisense; RMST, Rhabdomyosarcoma 2 associated transcript; RNCR2, retinal non-coding RNA 2; PINC, pregnancy-induced ncRNA; Tie-1AS, tyrosine kinase with immunoglobulin-like and EGF-like domains 1, antisense; Vax2os1, ventral anterior homeobox-containing gene 2 opposite strand transcript.