Complex interactions in EML cell stimulation by stem cell factor and IL-3

Abstract

Erythroid myeloid lymphoid (EML) cells are an established multipotent hematopoietic precursor cell line that can be maintained in medium including stem cell factor (SCF). EML cultures contain a heterogeneous mixture of cells, including a lineage-negative, CD34 + subset of cells that propagate rapidly in SCF and can clonally regenerate the mixed population. A second major subset of EML cells consists of lineage-negative. CD34 − cells that can be propagated in IL-3 but grow slowly, if at all, in SCF, although they express the SCF receptor (c-kit). The response of these cells to IL-3 is stimulated synergistically by SCF, and we present evidence that both the synergy and the inhibition of c-kit responses may be mediated by direct interaction with IL-3 receptor. Further, the relative level of tyrosine phosphorylation of various substrates by either cytokine alone differs from that produced by the combination of the two cytokines, suggesting that cell signaling by the combination of the two cytokines differs from that produced by either alone.

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

“…It has been documented that c-Kit is able to crosstalk with many growth factor and cytokine receptors [26][27][28]81]. For example, erythropoietin and SCF have synergistic effects on erythropoiesis.…”

“…Mutation of Y823 leads to increased c-Kit internalisation and degradation, suggesting a role for this site . Activation of these pathways is implicated in numerous cellular processes, such as gene transcription, cellular proliferation, differentiation, survival and adhesion [16][17][18][19][20][21][22][23][24][25][26][27]. Src homology region 2 domain-containing phosphatase-1 (SHP-1), Casitas b-lineage lymphoma (c-Cbl), SOCS and the protein kinase C signals (brown) are involved c-Kit downregulation.…”

“…c-Kit signalling pathways are not simple linear reactions, but, rather, integrated inputs from different pathways that determine the biological consequences in different cellular contexts. For instance, c-Kit crosstalks with the erythropoietin receptor or interleukin receptors to recruit common downstream signalling molecules, creating a method for modulating diverse physiological responses [26][27][28][29].…”

Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis

“…This cell line was derived from murine bone marrow 3,4 . When fed with different growth factors, EML cells can differentiate into erythroid, myeloid, and lymphoid cells in vitro 5 .…”

“…The two populations are similar in morphology and have similar levels of c-kit mRNA and protein 6 . Lin-SCA-CD34− cells are capable of propagating in media containing IL-3 instead of SCF 3 . Unveiling the key regulators in the EML cell fate decision will offer better understanding of cellular and molecular mechanisms in early developmental transition during hematopoiesis.…”