An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin
Stem cell factor (SCF) and erythropoietin (EPO) are two most recognized growth factors that play in concert to control in vitro erythropoiesis. However, exact mechanisms underlying the interplay of these growth factors in vitro remain unclear. We developed a mathematical model to study co-signaling...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/98640 http://hdl.handle.net/10220/17446 |
| _version_ | 1826119818593435648 |
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| author | Phan, Tran Hong Ha Saraf, Pritha Kiparissides, Alexandros Song, Hao Lim, Mayasari Mantalaris, Athanasios (Sakis) |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Phan, Tran Hong Ha Saraf, Pritha Kiparissides, Alexandros Song, Hao Lim, Mayasari Mantalaris, Athanasios (Sakis) |
| author_sort | Phan, Tran Hong Ha |
| collection | NTU |
| description | Stem cell factor (SCF) and erythropoietin (EPO) are two most recognized growth factors that play in concert to control in vitro erythropoiesis. However, exact mechanisms underlying the interplay of these growth factors in vitro remain unclear. We developed a mathematical model to study co-signaling effects of SCF and EPO utilizing the ERK1/2 and GATA-1 pathways (activated by SCF and EPO) that drive the proliferation and differentiation of erythroid progenitors. The model was simplified and formulated based on three key features: synergistic contribution of SCF and EPO on ERK1/2 activation, positive feedback effects on proliferation and differentiation, and cross-inhibition effects of activated ERK1/2 and GATA-1. The model characteristics were developed to correspond with biological observations made known thus far. Our simulation suggested that activated GATA-1 has a more dominant cross-inhibition effect and stronger positive feedback response on differentiation than the proliferation pathway, while SCF contributed more to the activation of ERK1/2 than EPO. A sensitivity analysis performed to gauge the dynamics of the system was able to identify the most sensitive model parameters and illustrated a contribution of transient activity in EPO ligand to growth factor synergism. Based on theoretical arguments, we have successfully developed a model that can simulate growth factor synergism observed in vitro for erythropoiesis. This hypothesized model can be applied to further computational studies in biological systems where synergistic effects of two ligands are seen. |
| first_indexed | 2024-10-01T05:06:20Z |
| format | Journal Article |
| id | ntu-10356/98640 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:06:20Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/986402020-03-07T11:35:28Z An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin Phan, Tran Hong Ha Saraf, Pritha Kiparissides, Alexandros Song, Hao Lim, Mayasari Mantalaris, Athanasios (Sakis) School of Chemical and Biomedical Engineering DRNTU::Engineering::Bioengineering Stem cell factor (SCF) and erythropoietin (EPO) are two most recognized growth factors that play in concert to control in vitro erythropoiesis. However, exact mechanisms underlying the interplay of these growth factors in vitro remain unclear. We developed a mathematical model to study co-signaling effects of SCF and EPO utilizing the ERK1/2 and GATA-1 pathways (activated by SCF and EPO) that drive the proliferation and differentiation of erythroid progenitors. The model was simplified and formulated based on three key features: synergistic contribution of SCF and EPO on ERK1/2 activation, positive feedback effects on proliferation and differentiation, and cross-inhibition effects of activated ERK1/2 and GATA-1. The model characteristics were developed to correspond with biological observations made known thus far. Our simulation suggested that activated GATA-1 has a more dominant cross-inhibition effect and stronger positive feedback response on differentiation than the proliferation pathway, while SCF contributed more to the activation of ERK1/2 than EPO. A sensitivity analysis performed to gauge the dynamics of the system was able to identify the most sensitive model parameters and illustrated a contribution of transient activity in EPO ligand to growth factor synergism. Based on theoretical arguments, we have successfully developed a model that can simulate growth factor synergism observed in vitro for erythropoiesis. This hypothesized model can be applied to further computational studies in biological systems where synergistic effects of two ligands are seen. 2013-11-08T04:30:47Z 2019-12-06T19:58:02Z 2013-11-08T04:30:47Z 2019-12-06T19:58:02Z 2013 2013 Journal Article Phan, T. H. H., Saraf, P., Kiparissides, A., Mantalaris, A., Song, H., & Lim, M. (2013). An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin. Bioprocess and biosystems engineering, 36(11), 1689-1702. 1615-7591 https://hdl.handle.net/10356/98640 http://hdl.handle.net/10220/17446 10.1007/s00449-013-0944-0 en Bioprocess and biosystems engineering |
| spellingShingle | DRNTU::Engineering::Bioengineering Phan, Tran Hong Ha Saraf, Pritha Kiparissides, Alexandros Song, Hao Lim, Mayasari Mantalaris, Athanasios (Sakis) An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title | An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title_full | An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title_fullStr | An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title_full_unstemmed | An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title_short | An in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| title_sort | in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin |
| topic | DRNTU::Engineering::Bioengineering |
| url | https://hdl.handle.net/10356/98640 http://hdl.handle.net/10220/17446 |
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