Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor

Zsebo, Krisztina M.; Williams, David A.; Geissler, Edwin N.; Broudy, Virginia C.; Martin, Francis H.; Atkins, Harry; Hsu, Rou Yin; Birkett, Neal C.; Okino, Kenneth H.; Murdock, Douglas C.; Jacobsen, Frederick W.; Langley, Keith; Smith, Kent; Takeish, Takashi; Cattanach, B.M.; Galli, Stephen J.; Suggs, Sid

doi:10.1016/0092-8674(90)90302-u

Cited by 1,358 publications

(568 citation statements)

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“…When the c-Kit receptor binds with human stem cell factor (SCF), also termed cKit ligand, which is produced by mesenchymal cells, it will augment the proliferation of primitive bone marrow progenitor cells and differentiated mast cells. [13][14][15] The fibroblast-like stem cells express the c-Kit, suggestive of mesenchymal differentiation. STRO-1 is a monoclonal antibody that has been shown to recognize all the clonogenic mesenchymal stem cells in human bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

Song

Kang

et al. 2004

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Aims To evaluate the involvement of multipotential stem and progenitor cells in the pathogenesis of pterygium. Methods Paraffin-embedded and snap-frozen primary pterygium (n ¼ 10) were serially sectioned and analysed immunohistochemically to determine the expression level of AC133 (marker for the primitive haematopoietic progenitors), CD34 (marker for the haematopoietic progenitor cells and endothelium), c-Kit (marker for haematopoietic and stromal progenitor cells), and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhaematopoietic progenitor cells). Results In all the primary pterygium, immunoreactivity of AC133 and STRO-1 was found in some of the epithelial and stromal cells, CD34 was observed in the vascular endothelium, and some scattered ovoidal cells were found in the subepithelial connective tissue. C-Kit was expressed mainly in the basal epithelium of the head portions, and some spindle-shaped stromal cells. There is no immunoreactivity of AC133, c-Kit, and STRO-1 in normal conjunctiva, whereas CD34 was mildly stained with vessel wall. Conclusion Multipotential stem and progenitor cells may be involved in the pathogenesis of pterygium through its differentiation into fibroblasts and vascular endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

Song

Kang

et al. 2004

Eye

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“…The proto-oncogene c-kit [7,8], which is a receptor for stem cell factor (SCF) [9][10][11][12][13][14], plays a critical role in early hematopoiesis. Mutations at the murine dominant-white spotting locus that maps to c-kit cause severe anemia [15].…”

Section: Introductionmentioning

confidence: 99%

Down‐modulation of c‐kit mRNA and protein expression by erythroid differentiation factor/activin A

et al. 1995

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“…Kit W/W-m mice possess a point mutation in the tyrosine kinase domain that inactivates the receptor in one allele and a mutation in the second allele that results in lack of receptor at the cell surface (Copeland et al, 1990;Zsebo et al, 1990). As a consequence, activation of c-kit signaling by kit ligand is greatly reduced in kit receptorexpressing cells in bone marrow of mutant mice.…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence, activation of c-kit signaling by kit ligand is greatly reduced in kit receptorexpressing cells in bone marrow of mutant mice. The ligand for the kit receptor is encoded by the Steel (Sl) locus and is referred to variously as kit ligand, steel factor, stem cell factor, or mast cell growth factor (Zsebo et al, 1990). Several variants of kit ligand are expressed in a cell-specific manner by mesenchymal stem cells, c-Kit AND BONE MARROW ADIPOSITY adipocyte precursors, fibroblasts, and osteoblasts (Gattei et al, 1996;Huss and Moosmann, 2002;Koma et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Membraneassociated kit ligand-deficient Kit Sl/Sl-d mice have a complete loss of function mutation (Sl) on one allele caused by 4-kb deletion in genomic DNA and a partial loss of function mutation (Sl-d) on the second allele. The transmembrane and cytoplasmic domains of membrane-associated kit ligand are absent, and a protein similar to the secreted kit ligand is produced, which binds to and activates kit receptor (Zsebo et al, 1990;Ashman, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Reduced c‐Kit Signaling on Bone Marrow Adiposity

Turner

Wong

Iwaniec

2011

The Anatomical Record

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c-Kit (CD117) is required for normal differentiation of osteoblasts from bone marrow stromal cells and for normal bone formation. Osteoblasts and adipocytes originate from a common progenitor cell, and a reciprocal relationship in differentiation of the two lineages is often observed. Therefore, the effects of abnormal c-kit signaling on bone marrow adiposity and adipocyte precursor pool size were evaluated in mouse strains with loss of function mutations in kit receptor or kit ligand. Additionally, to determine whether short-duration pharmacological disruption of kit signaling influences bone marrow adiposity, we administered the kit receptor antagonist gleevec (imatinib mesilate) for 1 week to middle aged (13-month-old) male rats known to have high levels of bone marrow fat. Compared to wild-type littermates, adipocytes were absent and adipocyte precursors greatly reduced in bone marrow from kit receptor-deficient Kit W/W-m mice. Administration of secreted kit ligand to membrane-associated kit ligand-deficient Kit Sl/Sl-d mice was ineffective in inducing bone marrow adipogenesis. These findings suggest that activation of kit receptor by the membrane-associated form of kit ligand is required for kit signaling to promote bone marrow adipogenesis in mice. Rats treated with gleevec had lower adipocyte density compared to age-matched controls, suggesting that kit signaling is required to maintain normal bone marrow adiposity. Taken together, our results indicate that c-Kit signaling plays an important but previously unsuspected role in regulating bone marrow adiposity. Anat Rec, 294:1126Rec, 294: -1134Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.Key words: hematopoietic stem cell; mesenchymal stem cell; adipocyte; mast cell; receptor tyrosine kinase; gleevec (imatinib mesilate)Osteoblasts and adipocytes are derived from a common bone marrow progenitor (Prockop, 1997;Vaananen, 2005;Valtieri and Sorrentino, 2008). The primary function of osteoblasts is well defined. Osteoblasts generate bone matrix to support bone growth, turnover, and remodeling. Additionally, osteoblasts have been reported to participate in hematopoietic stem cell mobilization from their bone marrow niche and to support hematopoiesis (Nagayoshi et al., 2006;Mayack and Wagers, 2008). In contrast, the physiological significance of adipocytes residing within bone marrow is less well defined.Most fat depots act as dynamic energy reservoirs to maintain circulating triglyceride and free fatty acid levels (Caserta et al., 2001). During severe caloric restriction, fat catabolism becomes an important source of energy and peripheral fat depots decline in mass. In contrast, severe caloric restriction is associated with increased bone marrow adiposity (Batista et al., 1988;Bohm, 2000;Cui et al., 2006;Duque, 2008;Bredella et al., 2009). Bone marrow adipocytes sequester and esterify fatty acids during starvation, a finding which has fostered the belief that the bone marrow fat depot does not function as an important energy reservoir for peripheral tissu...

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Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor

Cited by 1,358 publications

References 47 publications

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

Down‐modulation of c‐kit mRNA and protein expression by erythroid differentiation factor/activin A

Effect of Reduced c‐Kit Signaling on Bone Marrow Adiposity

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