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Table 1 Phenotypes resulting from the depletion of TETs in ectoderm, mesoderm, and endoderm lineages

From: Decoding the role of TET family dioxygenases in lineage specification

Lineage

System

TET isoform

Phenotype

References

Ectoderm

Human ESCs

TET1/2/3 triple knockout

Form fewer PAX6+ neuroectoderm cells

[14]

 

Neuron stem cells

Tet1 or Tet2 knockdown

Reduce proliferation of neuron stem cells

[90]

 

Cortex

Tet2 or Tet3 knockdown

Abnormal accumulation of cell clusters along the radial axis in the intermediate zone and ventricular zone

[34]

 

Cerebellar granule cells

Tet1/3 double knockdown

Impair dendritic arborization of cerebellar granule cells

[77]

 

Mouse ESCs

Tet3 knockout

Apoptosis of neuron progenitor cells and reduce terminal differentiated neurons

[24]

 

Neurons

Tet1 knockout

Increase hippocampal long-term depression and impair memory extinction

[75]

 

Neurons

Tet1 overexpression

Promote neurogenesis

[91]

 

Retinal neurons

Tet2/3 double knockout

Defects in retinal cells terminal differentiation

[92]

 

Cortical neurons

Tet2 knockdown

Reduce neuronal cells survival

[93]

 

Head

Tet1 mutation

Defects in neural tube closure

[94]

 

Eye and neural

Tet3 knockdown

Eye malformations and small head

[6]

 

Oligodendrocyte precursor cells

Tet1, Tet2, or Tet3 knockdown

Reduce mature oligodendrocytes

[95]

 

Olfactory sensory neurons

Tet3 overexpression

Disturb axon targeting and olfactory receptor expression

[47]

 

Dental pulp cells

TET1 knockdown

Prevent the proliferation and differentiation of dental pulp cells

[96]

Mesoderm

Hematopoietic stem cells

Tet2 knockout

Enhance self-renewal of hematopoietic stem cells, expansion of myeloid progenitors

[97]

 

Bone marrow cells

Tet2 knockdown

Enhance self-renewal of hematopoietic stem cells, expansion of myeloid progenitors

[31]

 

Hematopoietic stem cells

Tet2/3 double knockout

Loss of hematopoietic stem cell-derived blood cells

[98]

 

Human ESCs

TET2 knockdown

Impair hematopoietic cell differentiation

[27]

 

T cells

Tet2/3 double knockout

Form more iNKT cell in the young mice, and skew major population to NKT17 cells

[74]

 

Regulatory T cells

Tet2/3 double knockout

Less regulatory T cells in the spleen and lymph nodes

[86]

 

Regulatory T cells

Tet1/2 double knockout

Less regulatory T cells in the spleen and lymph nodes

[83]

 

T cells

Tet2 knockout

Impair Th1 and Th17 cells differentiation and cytokine genes induction

[38]

 

T cell

Tet2 knockout

Promote memory CD8+ T cells differentiation after viral infection

[99]

 

B cells

Tet2/3 double knockout

Block progenitor B cells differentiation and maturation

[7, 61]

 

Mast cells

Tet2 knockout

Impair mast cell differentiation, cytokine production, and proliferation

[85]

 

Erythroid cells

TET2 or TET3 knockdown

Delay differentiation of erythroid progenitors and regulate terminal differentiation

[84]

 

Bone marrow mesenchymal stem cells

Tet1/2 double knockout

Increase self-renewal of bone marrow mesenchymal stem cells and reduce osteogenic differentiation

[53]

 

Smooth muscle cell

TET2 overexpression

Convert fibroblasts to smooth muscle cells

[51]

 

Skeletal muscle myoblasts

Tet2 knockdown

Impair myoblast differentiation

[88]

 

Cardiomyocyte

Tet2 knockdown

Downregulate genes related to cardiac muscle contraction and cardiac muscle fiber development

[10]

Endoderm

Intestinal stem cell

Tet1 knockout

Form shorter intestine

[25]

 

T84 colon adenocarcinoma cells

Tet1 knockdown

Dysregulate genes related to cell membrane and extracellular space

[100]