Upregulation of Lineage Specific Receptors and Ligands in Multipotential Progenitor Cells is Part of an Endogenous Program of Differentiation

Just, Ursula; Friel, Jutta; Heberlein, Christoph; Tamura, Teruko; Baccarini, Manuela; Tessmer, Uwe; Klingler, Karl; Ostertag, Wolfram

doi:10.3109/08977199308991589

Cited by 22 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…M-CSF (Sigma, MuÈ nchen, Germany) was added at concentration of 2000 U/ml. Rat sera against vFms and mouse-c-Fms were used as described previously (Tamura et al, 1986;Just et al, 1993). Monoclonal antibodies against phosphotyrosine (4G10), against Mycepitope (9E10), anti c-Fms rabbit IgG were from Upstate Role of FMIP in macrophage and granulocyte differentiation T Tamura et al Biotechnology Incorporated (Lake Placid, NY, USA) or from Santa Cruz Biotechnology (Santa Cruz, USA), respectively.…”

Section: Cells and Antibodiesmentioning

confidence: 99%

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation

et al. 1999

Self Cite

View full text Add to dashboard Cite

Hematopoietic cell growth, di erentiation, and commitment to a restricted lineage are guided by a set of cytokines acting exclusively on cells expressing the corresponding cytokine receptor. The macrophage colony stimulating factor (M-CSF, also termed CSF-1) and its cognate receptor, the tyrosine kinase c-Fms, are essential for monocyte and macrophage development. The underlying molecular mechanism, however, is poorly understood. Here we identi®ed a novel Fms-interacting protein (FMIP, MW 78 kDa) which binds transiently via its Nterminal 144 residues to the cytoplasmic domain of activated Fms-molecules. Binding of FMIP was paralleled by rapid tyrosine phosphorylation within the binding domain which drastically reduced its ability to associate with Fms. Binding was speci®c as evidenced by co-immunoprecipitation and association with recombinant GST-Fms fusion proteins. No binding was observed with the tyrosine phosphorylated cytoplasmic domains of c-Kit, TrkA, c-Met, and the insulin receptor. The role of FMIP in hematopoietic di erentiation was studied in the bipotential myeloid progenitor cell line, FDC-P1Mac11. Overexpression of FMIP prevented M-CSF induced macrophage di erentiation. Instead, cells di erentiated into granulocytes. Our data suggest that the level of FMIP expression could form a threshold that decides about di erentiation either into macrophages or into granulocytes.

show abstract

Section: Cells and Antibodiesmentioning

confidence: 99%

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…Signaling by cytokines would be required for survival and proliferation. In addition, cytokine signaling would further result in the activation of factors that influence differentiation, e.g., expression of lineage-specific receptors (52,53). The final choice of fate would thus be determined by combinations between Notch and cytokine signaling and possibly other as yet unknown factors.…”

Section: Notch and Hemopoietic Cytokines Act Together To Direct Hemopmentioning

confidence: 99%

Notch Signaling Induces Multilineage Myeloid Differentiation and Up-Regulates PU.1 Expression

Schroeder¹,

Kohlhof²,

Rieber³

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Hemopoietic commitment is initiated by and depends on activation of transcription factors. However, it is unclear whether activation of lineage-affiliated transcription factors is extrinsically regulated by to date unknown agents or is the result of a cell autonomous program. Here we show that signaling by the Notch1 transmembrane receptor instructively induces myeloid differentiation of multipotent hemopoietic progenitor cells and concomitantly up-regulates the expression of the transcription factor PU.1. Transient activation of Notch1 signaling is sufficient to irreversibly reduce self-renewal of multipotent progenitor cells accompanied by increased and accelerated differentiation along the granulocyte, macrophage, and dendritic cell lineages. Activated Notch1 has no direct influence on apoptosis of multipotent progenitor cells, shows a weak inhibition of proliferation, and does not substitute for survival and proliferation signals provided by cytokines. Activated Notch1 directly increases PU.1 RNA levels, leading to a high concentration of PU.1 protein, which has been shown to direct myeloid differentiation. These findings identify Notch as an extrinsic regulator of myeloid commitment, and the lineage-affiliated transcription factor PU.1 as a specific direct target gene of Notch.

show abstract

“…These were selected with 400 mg/ml G418 (GIBCO BRL Life Technologies GmbH, Karlsruhe, Germany). G418 resistant clones were isolated and analyzed for expression of the corresponding CSF-1 cDNA by RT-PCR as described earlier (Just et al, 1993). Three independently isolated clones of each infected MMCE cell line expressing quantitatively equal amounts of CSF-1 mRNA were chosen and used for coculture experiments with hematopoietic cells.…”

Section: Cell Linesmentioning

confidence: 99%

Diverse isoforms of colony‐stimulating factor‐1 have different effects on the development of stroma‐dependent hematopoietic cells

Friel

Heberlein

Geldmacher

et al. 2005

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Maintenance and differentiation of hematopoietic stem and progenitor cells are controlled by complex interactions with the stroma microenvironment. Stroma-cell interactions can be supported by locally expressed membrane-spanning cell-surface (cs) growth factors. CSF-1 is expressed by stroma as a soluble glycoprotein, as proteoglycan, or as a membrane-spanning cs glycoprotein. CSF-1 regulates the survival, proliferation, and differentiation of mononuclear phagocytes. Whereas the biological role of soluble CSF-1 is well characterized, the function of the membrane-spanning cell-surface CSF-1 (csCSF-1) remains unclear. To analyze the biological significance of csCSF-1 in vitro, we used an epithelial cell line to ectopically express the different CSF-1 isoforms. In co-cultures of CSF-1 transduced epithelial cells with primary, early hematopoietic progenitor cells we examined whether interaction between csCSF-1 and its receptor mediates cell proliferation, self-renewal, or differentiation. csCSF-1 induces long-lasting proliferation of stimulated cells and furthermore supports self-renewal. Ectopic secretion of soluble CSF-1 does not permit long-term growth of progenitor cells but induces differentiation of monocytes into macrophages. Previously, we showed that the soluble and cs isoforms of stroma-encoded SCF differently affect the development of hematopoietic cells. Cell-surface SCF (csSCF) promotes self-renewal of stimulated cells whereas soluble SCF causes clonal extinction. These results and those presented here for CSF-1 provide evidence for diverse functions of the isoforms of the ligands SCF and CSF-1 for two tyrosine kinase receptors of the subclass III both regulating hematopoiesis on stroma.

show abstract

Upregulation of Lineage Specific Receptors and Ligands in Multipotential Progenitor Cells is Part of an Endogenous Program of Differentiation

Cited by 22 publications

References 28 publications

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation

Notch Signaling Induces Multilineage Myeloid Differentiation and Up-Regulates PU.1 Expression

Diverse isoforms of colony‐stimulating factor‐1 have different effects on the development of stroma‐dependent hematopoietic cells

Contact Info

Product

Resources

About