Display Settings:

Items per page

Results: 6

1.
Figure 3

Figure 3. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

Stat3 and Stat1 exhibit erythroid lineage specific expression.Stat3 (A) is expressed at low-levels only in the primitive erythroid lineage (white bars). In contrast, Stat1 (B) is preferentially expressed in the adult definitive erythroid lineage (black bars), with expression levels increasing as cells mature.

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.
2.
Figure 5

Figure 5. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

The molecular signature for IFN signaling is specific to the adult definitive erythroid lineage. In the microarray expression dataset, genes involved upstream (A) or downstream (B) of IFN-signaling were found to be preferentially expressed during adult definitive erythropoiesis. This includes Ifng and downstream apoptotic (Casp1, Tnfsf10) and anti-apoptotic genes (e.g., Bcl2l, Bcl2).

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.
3.
Figure 6

Figure 6. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

IFNγ differentially modulates definitive erythroid colony formation. Erythroid progenitor assays were performed on single-cell suspensions of dissociated murine E8.5 embryos (EryP-CFC) and adult bone marrow (CFU-E) in the presence or absence of IFNγ (10 ng/ml). CFU-E and EryP-CFC colonies were identified by morphologic criteria and scored at 2–3 and 5 days, respectively. Values for IFN-treated cultures are presented as normalized to vehicle-treated (phosphate buffer) control cultures.

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.
4.
Figure 1

Figure 1. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

Estimates of gene-essentiality inferred from expression and network topology discriminate key regulators of erythropoiesis. Erythroid lineage-specific estimates of ranked gene-essentiality were made for each transcription factor expressed in the erythropoiesis expression dataset. The distribution of scores in all three erythropoietic lineages (A: adult definitive; B: fetal definitive; C: primitive) are strongly right skewed. Known definitive regulators (indicated by black dots and stars) exhibit a bi-modal distribution, with essential and key regulators, including Klf1, Gata1 and Tal1 (black stars), falling in the right tail and non-essential factors (e.g., Nfia) falling near the distribution mode. Thus, right-tail genes in all distributions (S ≥1.8) most likely possess topological and expression properties most similar to those of the known essential regulators of adult definitive erythropoiesis.

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.
5.
Figure 2

Figure 2. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

Putative key regulators of primitive erythropoiesis are differential expressed in primitive versus adult definitive erythropoiesis. 144 genes in the right-tail of the distribution of estimated essentiality scores for the primitive erythroid lineage were found to be differentially expressed compared to the adult definitive erythroid lineage. These genes fall into 6 clusters: A) primitive: preferentially expressed late, definitive: steady-state expression at low levels or not expressed; B) primitive: steady-state expression at low levels or not expressed, definitive: preferentially expressed late; C) preferentially expressed in primitive proerythroblasts; D) primitive: preferentially expressed early and not expressed late, definitive: expression at low levels with some preferential expression in proerythroblasts; E) primitive: preferentially expressed early and not expressed late, definitive: preferentially expressed early and expressed late; and F) primitive: preferential expression early at low levels or not expressed, definitive: preferential expression early or high-levels of steady-state expression. Gene set enrichment analysis identified 56 genes activated downstream of MAPK signaling (†), 11 of which also are downstream effectors of EPO-induced signaling pathways (red). A high-quality version of this image with the heatmap assembled into a single column and cluster dendrogram is available in the Additional file 4: Figure S7.

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.
6.
Figure 4

Figure 4. From: Stat and interferon genes identified by network analysis differentially regulate primitive and definitive erythropoiesis.

Stat3 inhibition differentially affects primitive erythroblast maturation in vitro. Erythroid progenitor assays were performed on single-cell suspensions of individual, dissociated E8.5 embryos (A) and bone marrow (B,C) cultured in methylcellulose with appropriate media and cytokine supplementation. EryP-CFC (A) colonies were scored after 5 days, d3 BFU-E (B) were scored after 3 days and CFU-E (C) were scored after 2 – 3 days of culture. Primitive erythroblast maturation cultures were performed on cells pooled from dissociated E8.5 embryos (D) while definitive cultures were initiated with ESRE (E). All cultures were treated with DMSO as a vehicle control or 100 μM Stat3 inhibitor, S3I-201. Liquid cultures (D,E) were pretreated with DMSO or S3I-201 for 2 hours prior to EPO stimulation. Definitive erythroblasts are cultured for 2 days, versus 4 days for primitive erythroblasts, because of their more rapid maturation in vitro and in vivo. Images are representative of primitive erythroblasts at days 1 and 4 of culture (D) and definitive erythroblasts at days 0 and 2 of culture (E).

Emily Greenfest-Allen, et al. BMC Syst Biol. 2013;7:38-38.

Display Settings:

Items per page

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk