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SCF, often known as Kit Ligand, KITL or KITLG, is involved in pathways that control the regulation of cell survival, migration and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, and melanogenesis. SCF binding to the receptor-type protein-tyrosine kinase KIT, induces a cell signaling pathway that activates several other cell signaling pathways, including PIK3R1/AKT1, GRB2, RAS, RAF1, MAPK1/ERK2, MAPK3/ERK1, and STAT signaling events. The effects of SCF on these secondary pathways further allow it to play a role in many or the major cellular processes. The SCF, of most vertebrates, has a soluble form as well as the membrane bound type I receptor form. Mutations in the SCF pathway may result in a broad range of abnormalities including anemia, and sterility. SCF and KIT interaction has been shown to promote the growth of cancer cells and organoids in culture, and xenograft tumors in mice. SCF is being utilized in many animal model systems, from metastasis research in breast tumor-bearing arthritic mice to the genetic linkage to de-pigmentation in pigs. Interestingly, a second SCF pathway was retained in zebrafish, after a whole genome duplication, and is now undergoing divergent evolution.
Homology Across Species
Sus scrofa (pig) SCF – 100%
Camelus dromedarius (Arabian camel) SCF – 97%
Vicugna pacos (alpaca) SCF – 97%
​Camelus bactrianus (Bactrian camel) SCF – 97%
Generation of human endothelium in pig embryos deficient in ETV2.
Das S, Koyano-Nakagawa N, Gafni O, Maeng G, Singh BN, Rasmussen T, Pan X, Choi KD, Mickelson D, Gong W, Pota P, Weaver CV, Kren S, Hanna JH, Yannopoulos D, Garry MG, Garry DJ.
Nat Biotechnol. 2020 Mar;38(3):297-302. doi: 10.1038/s41587-019-0373-y. Epub 2020 Feb 24.
Applications: The proteins were used in a hematopoietic assay which used cells from embryoid bodies.
The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney1,2. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages3-7. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.
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