The Role of RNA Methylation in Regulating Stem Cell Fate and Function-Focus on m⁶A

Table 1

RNA methylation regulators and their functions in different types of stem cells.

Stem cell types	RNA methylation	Writer	Eraser	Reader	Related function	Reference
Embryonic stem cells (ESCs)	m^6A	METTL14			ESC stemness and differentiation	[35]
	m^6A; m^6A; m^6A	METTL3; METTL3, WTAP; METTL5			Naive pluripotency; ESC differentiation; ESC pluripotency and differentiation	[36]; [37]; [12, 38]
	m^6A	WTAP-Virilizer-Hakai			ESC self-renewal and differentiation	[39]
	m^6A	METTL3-METTL14-WTAP			Early cell fate determination and pluripotency	[70]
	m^6A		FTO		ESC pluripotency	[40]
	m^6A			YTHDF3	ESC pluripotency	[41]
	m^6A	METTL3		YTHDC1	Chromatin accessibility and transcription	[42]
	m^6A			YTHDF1/2/3	ESC differentiation	[43]
	m^5C	NSUN3			ESC proliferation and differentiation	[94]
	U-tail			DIS3L2	ESC differentiation	[101]
Hematopoietic stem cells (HSCs)	m^6A	METTL3			Cell differentiation and cell proliferation; Endothelial-to-hematopoietic transition; The maintenance of HSC identity and symmetric commitment	[47, 49–51]
	m^6A			YTHDF2	Endothelial-to-hematopoietic transition; HSC self-renewal	[51, 52]
	m^6A	METTL14			Terminal myeloid differentiation of normal HSPCs	[53]
Neural stem cells (NSCs)	m^6A	METTL3			Proliferation and differentiation of adult NSCs; Neuronal development and neurogenesis	[55]
	m^6A	METTL14			NSC proliferation and differentiation	[57]
	m^6A		FTO		Proliferation and neuronal differentiation of adult NSCs	[58, 59]
	m^6A			YTHDF2	Self-renewal, proliferation, and differentiation of NSCs	[60]
	m^5C	NSUN2			Migration and differentiation of neuroepithelial stem and progenitor cells	[95]
Bone marrow mesenchymal stem cells (BMSCs)	m^6A	METTL3			BMSC differentiation	[62–66]
	m^6A		FTO		MSC differentiation	[67]
	m^6A			YTHDF2	Adipogenesis	[62]
Induced pluripotent stem cells (iPSCs)	m^6A	METTL3		YTHDF1/YTHDF2	Self-renewal and pluripotency of iPSCs	[69, 72]
	m^6A	METTL3-METTL14-WTAP			Early cell fate determination and pluripotency	[70]
				YTHDF2; YTHDF3	iPSC reprogramming	[71]
	U-tail	TUT7			The neural differentiation of primed PSCs	[98]
Cancer stem cells (CSCs)	m^6A	METTL3			Myeloid leukemia cell differentiation and apoptosis; Maintenance of the leukemic state; Colorectal CSC stemness phenotype and metastasis of CRC; GSC maintenance and dedifferentiation of glioma cells; GSC growth, self-renewal, and tumor progression	[47, 74, 78, 80–83]
	m^6A	METTL14			Development and maintenance of AML self-renewal of leukemia stem and initiation cells; GSC growth, self-renewal, and tumor progression	[53, 83]
	m^6A			YTHDF2	The overall integrity of LSC function; GSC growth	[77, 88]
	m^6A			YTHDF1	CRC CSC marker expression; GBM tumorigenesis	[79, 87]
	m^6A		ALKBH5		LSC self-renewal and function; Self-renewal, proliferation, and tumorigenesis of GSCs; Radioresistance and invasiveness of GSCs; BCSC phenotypes and breast cancer metastasis	[75, 76, 84, 85, 91]
	m^6A		FTO		GSC growth, self-renewal, and tumor progression	[83, 86]
	m^6A			IGF2BP2	CRC stemness and metastasis	[78]
				IGF2BP1	Self-renewal and stemness maintenance of BCSCs	[92]
	U-tail			DIS3L2	CSC properties	[102]