Table 1 The survival signaling pathway in HFSCs

Wnt

Wnt/β-catenin

Wnt

up

Cyclin D1

Initiating DNA synthesis and leading to the increase of viability of HFSCs

[117]

Myc

Leading to the activation of HFSCs by increasing lactate production, and also increasing the viability of HFSCs

[117, 118]

Axin2

Contributing to proliferation, migration of dermal papilla and promoting HFs growth

[119]

Lef1

Activating target gene expression, promoting the activation, proliferation, and differentiation of HFSCs, increasing Shh level by leading to the downregulation of E-cadherin, and transmitting the early Wnt signals along with β-catenin

[6, 83, 120]

down

Dlx3

Leading to enhanced proliferation and delayed regression, since it is essential in hair morphogenesis, differentiation and cycling programs, and also leading to the loss of BMP signaling

[83]

Shh

Msi2-Shh-Gli1

SHH

up

Gli1

Leading to HFSCs proliferation and differentiation, and inducing HFs neogenesis and hair placode/germ formation

[3, 121]

Ptch1

Activating Gli1 transcription factors and leading to HFSCs proliferation and differentiation

[7]

Cyclin D1, Cyclin D2

Inducing the activation of HFSCs and leading to the increase of viability of HFSCs

[7, 117]

Sox9

Being required for SOX9( +) cell specification to HFSCs, leading to the production of Merkel cells in hair placode and maintaining the growth of HFs after morphogenesis

[122, 123]

Notch

NICD

up

Hey1

Leading to HFSCs proliferation

[99]

Hes1

Replenish HFSCs in order to maintain the hair cycle homeostasis and leading to the activation of the secondary hair germ

[124]

Hes5

Reducing HFSCs migration and clonogenicity

[125]

BMP

BMPR

up

PTEN

Inducing autophagy to facilitate HFSCs differentiation, inhibiting HFs hyperplasia and reducing the risk of tumorigenesis

[126, 127]

bHLH

Being able to encode ID proteins as mediators of HFSCs quiescence

[128]

down

Wnt7b

Leading to the disrupted HF cycling which manifests a shortening growth phase, premature catagen onset and shortening hair coat production with low-level expression of HFs differentiation markers

[129]

Lhx2

Leading to the delay of HFSCs activation

[83]

TGF-β

TGF-β/smad

TGF-β

up

Wnt

Contributing to promotion of cells cycle for HFSCs

[117]

β-catenin

Promoting the HFSCs proliferation and differentiation, and exerting long-term homeostasis of skin epithelia

[117, 120]

pSmad2

Promoting the transition between telogen and anagen

[130]

Tmeff1

Lowering the BMP threshold for HFSCs activation by mediating the inhibited effect of TGF-β2 on BMP signaling, and contributing in HFSCs activation during the telogen to anagen transition

[130]

EGFR

TGF-α/EGFR

EGFR

up

TGM

Leading to the differentiation of suprabasal-like KC and promoting cornified envelope formation

[131]

Flg

Leading to the differentiation of HFSCs and contributing to the epidermal barrier function

[132]

down

Keratin 1

Leading to the differentiation of suprabasal-like KC

[131]

Loricrin

Leading to the differentiation of suprabasal-like KC

[131]

Wnt4, 6, 7b, 10a, 10b

Being essential to restrain proliferation and support HFSCs numbers and their quiescence by influencing Wnt signal pathway

[133]

AKT

PI3K/AKT

AKT

up

TGF-β2

Leading to the activation of TGF-β mediated transcription in HFSCs and inducing HFSCs to proliferate during the quiescent period of the hair cycle

[130, 134]

IGFBP-3, 4, 24, and 25

Exerting both growth-inhibitory and -potentiating effects for HFSCs, and IGFBP4 acting as an inhibitor in the canonical Wnt pathway by directly interacting with the Wnt receptor to prevent Wnt3a binding

[134]

down

IGFR1 and IGFR2

Expressing a duality of HFSCs including both growth-inhibitory and -potentiating effects, and leading to delay in the anagen/catagen switch among HFs

[134, 135]

Fgf18

Leading to HFSCs proliferation and hair regeneration

[6, 8]

Foxp1

Leading to HFSCs proliferation and hair regeneration

[8]

Fox

Fox family protein

up

Cdh1

Weakening proliferative activity of Bu-HFSCs due to E-cadherin–mediated inter-SC adhesion

[136]

Lhx2

Leading to HFSCs activation, maintaining their characters of regeneration and undifferentiation in HFs, and also promoting epidermal regeneration

[83, 137,138,139]

LHX2

up

Sox9

Leading to HFSCs differentiation to promote epidermal regeneration in wound-healing process

[138]

Tcf4

Leading to HFSCs differentiation to promote epidermal regeneration in wound-healing process

[138]

down

Lgr5

Inhibiting the proliferation of HFSCs and disturbing the cycling of anagen HFs

[127, 138]