Proliferation Inhibition of Murine Pluripotent Haemopoietic Stem Cells By Interferon Or Poly I:C

Abstract

The effect of mouse serum interferon (IF) in vitro and an inducer in vivo on the proliferation of a pluripotent stem cell population with high turnover rate was studied. Proliferation rate was characterized by the number of CFUs in the S phase of the cell cycle. Increased proliferation of bone marrow stem cell populations was produced either by irradiating the donor mice with 3·36 Gy (336 rad) 60Co‐gamma rays 7 days before the experiment or by incubating normal bone marrow cells with 10–11 M concentration of isoproterenol. IF considerably reduced the number of CFUs in S phase in both cases without reducing the CFUs content of the samples. Injection of IF inducer (4 mg/kg poly I:C) into regenerating mice also inhibited the proliferation of CFUs without decreasing the femoral CFUs level. Regeneration kinetics of CFUs from irradiated poly I:C‐treated mice ran parallel with that of irradiated untreated animals but showed a characteristic delay corresponding to approximately one CFUs doubling. A transient, non‐cytotoxic proliferation inhibitory effect of IF or IF inducer is, therefore, proposed.

Potential Pitfalls of the Mx1-Cre System: Implications for Experimental Modeling of Normal and Malignant Hematopoiesis

“…The Mx1 - Cre system can be potentially associated with additional problems. For instance, pIpC administration has been suggested to trigger HSC cycling, similar to interferon itself ( Essers et al., 2009 , Gidali et al., 1981 , Sugiyama et al., 2006 ). While we found less evidence for a dramatic effect of pIpC in inducing HSPC proliferation, we noted that pIpC induced rapid and transient changes (that resolved by day 8) in cellular phenotypes, which could affect the interpretation of experimental results.…”

Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches

“…pIpC reversibly inhibited expansion of primitive hematopoietic cells, probably reflecting a transient antiproliferative and/or apoptotic effect of interferon induced by pIpC treatment (Gidali et al, 1981). In addition, the numbers of CD34 2 c-kit + Sca-1 + Lin 2 and SP low cells were reduced in pIpC-treated wild-type and control MxCre-CXCR4 f/wt mice as well as MxCre-CXCR4 f/null mice at early time points after injection of pIpC (see Figure S1 in the Supplemental Data available online and data not shown).…”

Yin and Yang: The dual effects of interferons on hematopoiesis

“…As in mice, loss of IFN signaling did not affect EMP numbers in zebrafish embryos [21], highlighting the specificity of IFNs on HSC and LP development. In addition, zebrafish morphants lacking IFN or its receptor had reduced expression of runx1, an important marker of HSPCs in the AGM region [27], thus supporting the significance of IFN in HSC emergence across species. Furthermore, Sawamiphak et al showed that IFN overexpression was sufficient to rescue loss of HSCs in two models (Notch signaling knockdown and blood loss) [27].…”

“…In addition, zebrafish morphants lacking IFN or its receptor had reduced expression of runx1, an important marker of HSPCs in the AGM region [27], thus supporting the significance of IFN in HSC emergence across species. Furthermore, Sawamiphak et al showed that IFN overexpression was sufficient to rescue loss of HSCs in two models (Notch signaling knockdown and blood loss) [27]. Similarly, zebrafish embryos lacking the IFN ortholog (IFNφ) had fewer HSPCs and thymocytes, whereas knockdown of Irf2a, a negative regulator of IFN signaling, had more of these cells.…”