Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation

Abstract

Mammalian transcriptome analysis has uncovered tens of thousands of novel transcripts of unknown function (TUFs). Classical and recent examples suggest that the majority of TUFs may underlie vital intracellular functions as non-coding RNAs because of their low coding potentials. However, only a portion of TUFs have been studied to date, and the functional significance of TUFs remains mostly uncharacterized. To increase the repertoire of functional TUFs, we screened for TUFs whose expression is controlled during differentiation of pluripotent human mesenchymal stem cells (hMSCs). The resulting six TUFs, named transcripts related to hMSC differentiation (TMDs), displayed distinct transcriptional kinetics during hMSC adipogenesis and/or osteogenesis. Structural and comparative genomic characterization suggested a wide variety of biologically active structures of these TMDs, including a long nuclear non-coding RNA, a microRNA host gene and a novel small protein gene. Moreover, the transcriptional response to established pathway activators indicated that most of these TMDs were transcriptionally regulated by each of the two key pathways for hMSC differentiation: the Wnt and protein kinase A (PKA) signaling pathways. The present study suggests that not only TMDs but also other human TUFs may in general participate in vital cellular functions with different molecular mechanisms.

Inhibitory effects of high stability fucoxanthin on palmitic acid-induced lipid accumulation in human adipose-derived stem cells through modulation of long non-coding RNA

“…It is claimed that several non-coding named transcripts related to hMSC differentiation (TMDs) display distinct transcriptional kinetics during hMSC adipogenesis and/or osteogenesis. 36 Using Microarray or RNA Profiling technology, some studies showed that various lncRNA transcripts are functioning in adipogenesis. 11,37 However, there are extremely few investigations on how food affects lncRNA expression during lipid accumulation.…”

Reconstruction of human elastic cartilage by a CD44 + CD90 + stem cell in the ear perichondrium

“…These steps were repeated twice with an interval of 1 wk. We also tested the adipogenic and osteogenic potential of perichondrocytes as previously described (37).…”

Emerging roles for long noncoding RNAs in skeletal biology and disease

“…For example, XIST is named for “X (Inactive)-Specific Transcript” (16,17), while DANCR stands for “Differentiation Antagonizing Non-Protein Coding RNA” (18–20). However, when IncRNAs are initially identified without a known function, they are named based on the associated genomic context or assigned an arbitrary name based on the GENCODE categorization, which divides IncRNAs into the following sub-categories (21,22):

Antisense: IncRNA whose sequence overlaps the exonic sequence of a protein-coding gene on the opposite strand (e.g., HIF1a-AS1 )

lincRNA: IncRNA located within the intergenic regions of protein-coding genes (e.g., LINC00152 )

Sense-overlapping: IncRNA whose intronic sequences encode a protein-coding or noncod-ing gene without overlap of exonic sequences (e.g., SOX2-OT )

Sense intronic: IncRNA residing within introns of a coding gene (e.g., SPRY-IT1 )

Processed transcript: IncRNA that does not contain an ORF and does not fit in any of the above categories

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