Kitl, also known as stem cell factor (SCF), is a paracrine signaling factor playing crucial roles in multiple biological processes. It is involved in maintaining tissue homeostasis, regulating hematopoiesis, and influencing cell proliferation, differentiation, and self-renewal. Signaling through Kitl is important in pathways related to melanocyte development, ovarian folliculogenesis, and the maintenance of hematopoietic stem cells (HSCs) [1,4,5,6]. Genetic models, especially mouse models, have been valuable in studying Kitl's functions.

In mice, conditional deletion of Scf (Kitl) from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells depleted HSCs from the bone marrow, indicating that these cell types expressing Kitl are crucial for HSC maintenance [6]. In pancreatic tissue, loss of mesenchymal Kitl during tumorigenesis promoted tumor growth and reduced survival of tumor-bearing mice, suggesting that Kitl signaling helps maintain pancreas tissue architecture and restrains tumor progression [2,3]. Overexpression of Kitl in mice influenced melanocyte proliferation, differentiation, and the self-renewal of melanocyte stem cells, with a single pulse of Kitl transgene expression in postnatal mice having long-lasting effects on pigmented skin cells [5].

In conclusion, Kitl is essential for maintaining tissue homeostasis in various organs, such as the bone marrow, pancreas, and skin. Mouse models, especially those with gene knockout or conditional knockout of Kitl, have revealed its significant role in hematopoietic stem cell maintenance, pancreas tumor progression, and melanocyte-related processes. These findings contribute to our understanding of related diseases, including hematopoietic disorders and pancreatic cancer [1,2,3,6].

References:

1. Young, Kira A, Telpoukhovskaia, Maria A, Hofmann, Johanna, Kokkaliaris, Konstantinos D, Trowbridge, Jennifer J. . Variation in mesenchymal KITL/SCF and IGF1 expression in middle age underlies steady-state hematopoietic stem cell aging. In Blood, 144, 378-391. doi:10.1182/blood.2024024275. https://pubmed.ncbi.nlm.nih.gov/38598841/

2. Oñate, Maria Kathrina, Oon, Chet, Bhattacharyya, Sohinee, Xia, Zheng, Sherman, Mara H. . Stromal KITL/SCF Maintains Pancreas Tissue Homeostasis and Restrains Tumor Progression. In Cancer discovery, 15, 913-929. doi:10.1158/2159-8290.CD-24-1079. https://pubmed.ncbi.nlm.nih.gov/39918337/

3. Oñate, M Kathrina, Oon, Chet, Bhattacharyya, Sohinee, Xia, Zheng, Sherman, Mara H. 2024. Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.07.29.605485. https://pubmed.ncbi.nlm.nih.gov/39131374/

4. França, Monica Malheiros, Mendonca, Berenice Bilharinho. 2021. Genetics of ovarian insufficiency and defects of folliculogenesis. In Best practice & research. Clinical endocrinology & metabolism, 36, 101594. doi:10.1016/j.beem.2021.101594. https://pubmed.ncbi.nlm.nih.gov/34794894/

5. Aoki, Hitomi, Tomita, Hiroyuki, Hara, Akira, Kunisada, Takahiro. 2023. Postnatal Expression of Kitl Affects Pigmentation of the Epidermis. In The Journal of investigative dermatology, 144, 96-105.e2. doi:10.1016/j.jid.2023.06.200. https://pubmed.ncbi.nlm.nih.gov/37482288/

6. Ding, Lei, Saunders, Thomas L, Enikolopov, Grigori, Morrison, Sean J. 2012. Endothelial and perivascular cells maintain haematopoietic stem cells. In Nature, 481, 457-62. doi:10.1038/nature10783. https://pubmed.ncbi.nlm.nih.gov/22281595/