SCGF but not SCF
supports proliferation
of ES cells.
SCGF is a novel innate
immune protector
against infection.
NF-κB regulates scgf positively or
negatively?
SCGF interactome:
Sav1, Cep85, Traf2/7,
XIAP
SCGFR
What function does
exosomal SCGF carry
out?
Is SCGF a
transcriptokine
bifunctioning as
cytokine and
intracellular regulator?
SCGF, a therapeutic
target for cancer and
leukemia cells
What type of sugar
does SCGF bind?
“SCGF pretends to be a useless lamp in the daytime, but changes to be a powerful rescue light at blackout”
New Unravelment ! We launch a new era in SCGF research. Several noteworthy findings have recently been reported.
When resting chondrocytes in PTHrP-creER; Ptch1fl/flcKO
mice are specifically activated for Hedgehog signaling, their
PTHrP and scgf-upregulated skeletal stem cells
differentiate in a stepwise manner to osteoblasts (698). (See also"Biologic Function"section in details)
SCGF has a proliferative activity on human and mouse pancreatic islet cells. Lipotoxic stress, e.g. high fat diet-induced obesity and in vitro treatment with palmitic acid, down-regulates scgf gene expression in mouse pancreatic islet cells to suppress their proliferation (609). rh/rmSCGF mitigates the lipotoxicity on islet cells, and further stimulates islet stellate and β cell proliferation. rhSCGF promotes proliferation of human β cells with facilitated insulin secretion (691). (See also"Biologic Function"section in details)
SCGF promotes viability and proliferation of mouse female
germline stem cells (FGSCs).
rmSCGF, or daidzein through scgf up-regulation, activates
Akt signaling pathway to promote viability and proliferation
of mouse FGSCs in vitro (680). (See also“Biologic Function” and “Gene Expression”section in
details)
SCGF has a survival activity on human B cells.
Monocyte-secreted SCGF promotes human B cell survival
alone and synergistically with BAFF (678). (See also“Biologic Function” section in details)
SCGF promotes tumor growth.
SCGF secreted by cancer cells exerts integrin-mediated
chemotactic activity on ambient vascular endothelial cells
and promotes tumor growth with enhanced angiogenesis
(671). SCGF suppression could open the way to a novel anti-cancer therapy.
(See also“Biologic Function” and “Disease” section in details)
SCGF restores stress-induced hematopoietic defect.
MAPK and NFκB-activated CDH5-MAPK mice exhibit
hematopoietic defect with perivascular niche inflammation.
Mouse SCGF restores hematopoietic and vascular defects
when administered to CDH5-MAPK mice or irradiated wild
type mice (616,Pat34). (See also“Biologic Function”and “Disease”section in details)
Serum SCGF level determines onset of SARS-CoV-2
infection.
Machine learning indicates with 100% accuracy that SARS-
CoV-2-infected patients with higher and lower serum SCGF
level are asymptomatic and symptomatic respectively
(632). SCGF is a prognostic biomarker for symptom onset
and, more importantly, SCGF could control novel protective
immune mechanisms against infection. As for 2018-2019
outbreak of Andes orthohantavirus pulmonary syndrome in
Argentina, reduced serum SCGF level is associated with
hantavirus spreaders compared to non-spreaders, and
among spreaders, notably with superspreaders compared to
non-superspreaders (636). Like SARS-CoV-2 infection
SCGF could be a critical player of innate immunity against
hantavirus infection. (See also“Disease” and “Perspectives” section in details)
Mouse scgf induces fetal osteogenesis. Androgenetic haploid mouse ES cells with scgf-targeted mutagenesis are injected into mature oocytes to yield scgf-/-or chimeric scgf+/-mice (604). The scgf-mutated newborn mice exhibit bone abnormalities, e.g. size reduction, impaired calcification and hypoplastic skull. Mouse scgf exerts osteogenic activity during fetal development. (See also"Biologic Function"section in details)
SCGF has been thought to bind integrins (ITGs) through
RGD motif sequence. Of human ITGα4β1, α9β1,
α10β1, α11β1, αVβ1, αVβ3, αIIbβ3 and αMβ2
tested, human SCGF selectively binds ITGα10β1 and
ITGα11β1 with similar high affinity as human pro-collagen
1αthrough RGD (594). Mouse SCGF acts on human and
mouse MSCs to induce osteogenic differentiation despite
lacking RGD through activated Wnt signal transduction, i.e.
phosphorylation of GSK3, accumulation of nuclear β-
catenin and up-regulation of Wnt target genes of Alp, Axin2,
Lef1 and Runx2. ITGα10β1 and ITGα11β1 are not RGD-
recognizing integrins and mouse SCGF lacks RGD, indicating
that SCGF binds integrins through other mechanisms than
RGD.
Scgf is a mandatory driver for MSC proliferation. Scgf gene
expression is highly down-regulated in the RelA-/- (a
component of NFκB) hES cell-derived MSCs, and they
exhibit defective self-renewal ability (592). Knockdown of
wild type hMSCs with scgf shRNA abrogates their
proliferative potential.
SCGF (Stem Cell Growth Factor) is a cytokine of the
C-type lectin family to foster and grow various kinds of stem cells,
e.g. embryonic stem (ES) cells, mesenchymal stem cells (MSCs),
hematopoietic stem cells (HSCs), neural stem cells (NSCs),
mammary stem cells, prostatic stem cells, etc.
SCGF is produced and secreted by stem cells themselves
through an autocrine mechanism or ambient stem cell niche cells
through a paracrine mechanism, e.g. osteoblasts and chondroblasts
in the bone marrow.
A confusable terminology of "stem cell growth factor" is
classified as follows;
In a narrow or specific sense: (Note! Distinguish scgf from KL)
Official gene name
Alias
Symbol
Full name
scgf
stem cell growth factor
clec11a
KL
c-kit (CD117) ligand
SCF (stem cell factor)
SLF (Steel factor)
Mast/stem cell growth factor
In a broad sense:
Growth factors for stem cells, including BMP, FGF, LIF and SCGF
This page aims at depicting everything about SCGF based on the
findings obtained so far, and is weekly updated along with undergoing
studies.
