Stem Cell Factor and Hematopoiesis

Broudy, Virginia C.

doi:10.1182/blood.v90.4.1345

Cited by 727 publications

(177 citation statements)

References 286 publications

(55 reference statements)

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“…FK228 enhances the generation of CD36 + GPA low cells from CD34 + cells in the presence of IL-3 and SCF + IL-3 poulou et al, 1993; Broudy, 1997). We first examined the effect of increasing concentrations of FK228 on the generation of CD36 + erythroid, CD14 + monocytic, and CD15 + granulocytic cells from CD34 + cells in serum-free suspension cultures in the presence of SCF + IL-3.…”

Section: Resultsmentioning

confidence: 99%

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

et al. 2006

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Summary Histone acetylation and deacetylation play fundamental roles in transcriptional regulation. We investigated the role of histone deacetylases (HDACs) in human adult haematopoiesis, using the structurally distinct HDAC inhibitors FK228 (depsipeptide) and Trichostatin A. When CD34+ cells were cultured with interleukin (IL)‐3 or stem cell factor (SCF) + IL‐3, FK228 (0·5 ng/ml) specifically enhanced the generation of immature erythroid cells with a CD36+ glycophorin A (GPA)low phenotype. In semisolid cultures, FK228 promoted the formation of erythroid colonies by CD34+ cells with IL‐3 and SCF + IL‐3. Furthermore, upon exposure to FK228, CD34+ cell‐derived CD36+GPA− cells were induced to form erythroid colonies with IL‐3 alone. Conversely, FK228 inhibited the generation of CD36+GPAhigh relatively mature erythroid cells from CD34+ cells in the presence of erythropoietin (EPO) and SCF + EPO. FK228 suppressed the EPO‐mediated survival of CD36+GPAlow/‐and CD36+GPAhigh cells and induced their apoptosis. Similar effects were observed for trichostatin A in the generation of erythroid cells in IL‐3‐ and EPO‐containing cultures. These data suggest that HDACs negatively regulate the IL‐3‐mediated growth of early erythroid precursors by suppressing their responsiveness to IL‐3, while playing an important role in EPO‐mediated differentiation and survival of erythroid precursors. Our data revealed that HDACs have diverse functions in human adult erythropoiesis.

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Section: Resultsmentioning

confidence: 99%

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

et al. 2006

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“…In the embryo, Kitl is expressed at hematopoietic sites [25][26][27], though the cells responsible for its production in the embryonic hematopoietic niche have not been identified. Genetic defects in Kitl/Kit signaling result in late embryonic/perinatal lethality with severe anemia [22,28]. This has been ascribed to an erythroid differentiation block in > E13.5 FL, along with a decrease in FL CFU-S and neonatal HSCs [22,[28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

et al. 2018

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Few studies report on the in vivo requirement for hematopoietic niche factors in the mammalian embryo. Here, we comprehensively analyze the requirement for Kit ligand (Kitl) in the yolk sac and aorta–gonad–mesonephros (AGM) niche. In‐depth analysis of loss‐of‐function and transgenic reporter mouse models show that Kitl‐deficient embryos harbor decreased numbers of yolk sac erythro‐myeloid progenitor (EMP) cells, resulting from a proliferation defect following their initial emergence. This EMP defect causes a dramatic decrease in fetal liver erythroid cells prior to the onset of hematopoietic stem cell (HSC)‐derived erythropoiesis, and a reduction in tissue‐resident macrophages. Pre‐HSCs in the AGM require Kitl for survival and maturation, but not proliferation. Although Kitl is expressed widely in all embryonic hematopoietic niches, conditional deletion in endothelial cells recapitulates germline loss‐of‐function phenotypes in AGM and yolk sac, with phenotypic HSCs but not EMPs remaining dependent on endothelial Kitl upon migration to the fetal liver. In conclusion, our data establish Kitl as a critical regulator in the in vivo AGM and yolk sac endothelial niche.

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“…Activation of KIT by KITLG leads to receptor dimerization and autophosphorylation of specific tyrosine residues in the kinase domain, and the activated downstream signal transduction induces KIT-mediated cellular action (Linnekin 1999). KIT signaling is required for the normal development of migratory cell populations of melanocytes, blood cells and primordial germ cells, and mutations in these loci result in pleiotropic developmental defects that affect pigment cells, hematopoietic cells, germ cells and interstitial cells of Cajal in the intestine (Broudy 1997; KITLG, respectively. Thus far, 88 and 48 phenotypic alleles have been identified in W and Sl loci, respectively (http://www.informatics.jax.org/searches/ allele_report.cgi?_Marker_key=10603; http://www.…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms of the KIT and KITLG genes in pigs

Okumura¹,

Matsumoto²,

Hamasima

et al. 2008

Animal Science Journal

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Here, we report the variability in the KIT tyrosine kinase receptor and its ligand KITLG genes by determining single nucleotide polymorphisms (SNPs) in 384 individuals including 11 pig breeds, two synthetic‐line cross pigs, two cross breeds, and one Japanese wild boar. SNPs and indels within the coding sequence regions of KITLG and KIT and their 5′‐flanking regions were detected by aligning sequences from eight pigs, and subsequently the SNPs were genotyped using matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI TOF‐MS). Principal component analysis using allele frequencies in the SNP locus showed a distant relationship between Asian and Euro‐American pig groups, except for Berkshire and Tokyo X breeds. These breeds were located within the mid‐portion of the distribution in the first principal component. The Hampshire breed was distant from the other pig groups on the axis of the second principal component. Haplotype frequencies that were deduced using non‐synonymous substitutions of the KIT gene revealed the uniqueness of Landrace, Large White, Middle White, and three‐way cross pigs (LWD) and of the Hampshire breed. On the other hand, the haplotypes of KITLG and KIT detected in the Berkshire breed were prevalent in Asian pig groups. This tendency is different from that observed in other Euro‐American pig breeds.

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Stem Cell Factor and Hematopoiesis

Abstract: During embryonic life, SCF and c-kit receptor RNA are 98195-7710.

Cited by 727 publications

References 286 publications

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

Single nucleotide polymorphisms of the KIT and KITLG genes in pigs

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