Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis

Table 1 Genes that undergo splicing events in stem cells and stem-like cancer cells

Type	Gene	Ensembl ID	Alternative RNA splice variants	Activities	Ref.
Non-cancerous stem cell	IGF1	ENSG00000017427	IGF1Ec, IGF1 Ea	IGF-IEc enhances proliferation and represses muscle progenitors differentiation, IGF-IEa activates anabolic pathways	[99]
	POU5F1 (OCT4)	ENSG00000204531	OCT4A, OCT4B, OCT4B1	Play roles in pluripotency and self-renewal of embryonic stem cells	[38]
	RBM4, RBM14, CoAA	ENSG00000173933	CoAZ, ncCoAZ	Influence co-transcriptional splicing	[100]
	DNMT3B	ENSG00000088305	DNMT3B3, DNMT3B3∆5	DNMT3B3∆5 expressed in ESCs and functionally distinct from DNMT3B3	[101]
	VEGFA	ENSG00000112715	VEGF120, VEGF164, VEGF188	All promote MSC proliferation; some enhance paracrine signaling, osteogenic, or endothelial differentiation	[102]
	FGF4	ENSG00000075388	FGF4, FGF4si	FGF4 is important to stem cell maintenance, while FGFsi antagonizes some of FGF4’s activity	[37]
	PKCd	ENSG00000163932	PKCdI, PKCdII	PKCdI is caspasecleavable and PKCdII is caspase in-cleavable	[103]
	POU2F2 (OCT2)	ENSG00000028277	OCT2.2, OCT2.4	Oct2.2 is sufficient to induce neural differentiation in mouse ESCs, Oct2.4 is able to block neural differentiation	[104]
	RMB14, CoAA	ENSG00000239306	CoAA, CoAM	CoAA is downregulated in favor of CoAM during early embryonic development	[105]
	RUNX1	ENSG00000159216	RUNX1a	Increases the capacity of the HSC pool	[41]
	Qki	ENSG00000112531	Qki5	Regulates neural stem cell function	[45]
	PTB	ENSG00000117569	nPTB (PTBP2) with exon 10	Transition of stem cell to neuron cells	[46]
	FOXP1	ENSG00000114861	FOXP1-ES	Promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells into induced pluripotent stem cells	[35]
Cancer stem cell	NUMB	ENSG00000133961	NUMB exon skipping by EMT	Affect the balance between stem-like and non-stem cancer cells	[67]
	KRAS	ENSG00000133703	KRAS4A	Enriched in the cancer stem cell population and helps to modulate the metabolic requirements and stress responses associated with the cancer stem-progenitor cell transition	[70]
	HER2	ENSG00000141736	D16her2	Role in the regulation of the BC stem cells (BCSCs) activity through its functional interaction with the NOTCH family members	[72]
	CD44	ENSG00000026508	CD44s	CD44s isoforms in cancer cells induces stem-like features	[79]
	CD44	ENSG00000026508	CD44v	Promote CSC activities and protecting CSCs from ROS-induced stress	[86]
	α6β1 integrin (ITGA5, VLA-6, CD49f/CD29)	ENSG00000091409	α6Bβ1 integrin	Promotes the function of breast CSCs and tumor initiation	[89]
	FLNB	ENSG00000136068	FLNB exon 30 skipping	Associated with EMT gene signatures in basal-like breast cancer/ establishing the mesenchymal and stem-like cell state in breast cancers	[75]
	DCLK1	ENSG00000133083	DCLK1-long isoforms (Isoforms 2 and 4)	Promotes expression of RCC stem cell markers and increases self-renewal activity	[98]
	POU5F1 (OCT4)	ENSG00000204531	OCT4A	Promotes stemness properties in embryonal carcinoma cells	[38]
	ALDH1	ENSG00000165092	ALDH1A1	Promotes tumorigenesis, mortality, and self-renewal activity in RCC	[98]

IGF-1: Insulin like growth factor 1; POU5F1: POU domain proteins; OCT4: Octamer-binding transcription factor 4; RMB: RNA binding motif protein; DNMT3B: DNA methyltransferase 3 beta; VEGFA: Vascular endothelial growth factor A; FGF4: Fibroblast growth factor 4; PKCd: Protein kinase C delta; RUNX1: RUNX family transcription factor 1; Qki: Isoforms of Quaking; PTB: Polypyrimidine tract binding; FOXP1: Forkhead box p1; NUMB: NUMB endocytic adaptor protein; KRAS: Kirsten rat sarcoma viral oncogene homolog; HER: Erb-B2 receptor tyrosine kinase; CD: Cluster of differentiation; ITGA5: Integrin subunit alpha 5; FLNB: Filamin B; DCLK1: Doublecortin-like kinase 1; ALDH1: Aldehyde dehydrogenase 1.