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...

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Main Authors: Phan, Tran Hong Ha, Saraf, Pritha, Kiparissides, Alexandros, Song, Hao, Lim, Mayasari, Mantalaris, Athanasios (Sakis)
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/98640
http://hdl.handle.net/10220/17446
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.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
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Engineering::Bioengineering
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
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.
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)
format Article
author Phan, Tran Hong Ha
Saraf, Pritha
Kiparissides, Alexandros
Song, Hao
Lim, Mayasari
Mantalaris, Athanasios (Sakis)
author_sort Phan, Tran Hong Ha
title 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_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_sort in silico erythropoiesis model rationalizing synergism between stem cell factor and erythropoietin
publishDate 2013
url https://hdl.handle.net/10356/98640
http://hdl.handle.net/10220/17446
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