Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

Fetal stem cells isolated from umbilical cord blood (UCB) possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of ther...

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Autores principales:	Biaoru Li, Lianghao Ding, Chinrang Yang, Baolin Kang, Li Liu, Michael D Story, Betty S Pace
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ecdc86b62484926923b5e0eb63f49d8
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spelling	oai:doaj.org-article:1ecdc86b62484926923b5e0eb63f49d82021-11-25T06:00:59ZCharacterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.1932-620310.1371/journal.pone.0107133https://doaj.org/article/1ecdc86b62484926923b5e0eb63f49d82014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107133https://doaj.org/toc/1932-6203Fetal stem cells isolated from umbilical cord blood (UCB) possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs) associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs) with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1) and 30 TFs were activated by day 56 (Profile-2). Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1) and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34+ stem cells including prolonged γ-globin expression combined with unique TFNs support novel mechanisms controlling the γ/β-globin switch during UCB-derived erythropoiesis.Biaoru LiLianghao DingChinrang YangBaolin KangLi LiuMichael D StoryBetty S PacePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107133 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Biaoru Li Lianghao Ding Chinrang Yang Baolin Kang Li Liu Michael D Story Betty S Pace Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
description	Fetal stem cells isolated from umbilical cord blood (UCB) possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs) associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs) with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1) and 30 TFs were activated by day 56 (Profile-2). Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1) and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34+ stem cells including prolonged γ-globin expression combined with unique TFNs support novel mechanisms controlling the γ/β-globin switch during UCB-derived erythropoiesis.
format	article
author	Biaoru Li Lianghao Ding Chinrang Yang Baolin Kang Li Liu Michael D Story Betty S Pace
author_facet	Biaoru Li Lianghao Ding Chinrang Yang Baolin Kang Li Liu Michael D Story Betty S Pace
author_sort	Biaoru Li
title	Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
title_short	Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
title_full	Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
title_fullStr	Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
title_full_unstemmed	Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.
title_sort	characterization of transcription factor networks involved in umbilical cord blood cd34+ stem cells-derived erythropoiesis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1ecdc86b62484926923b5e0eb63f49d8
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Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

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