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

Biaoru Li, Lianghao Ding, Chinrang Yang, Baolin Kang, Li Liu, Michael D. Story, Betty S. Pace

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 b-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 c/b-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 c/b-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 c/b-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 c-globin regulation. The characteristics of erythroblasts derived from UCB-CD34+ stem cells including prolonged c-globin expression combined with unique TFNs support novel mechanisms controlling the c/b-globin switch during UCB-derived erythropoiesis.

Original languageEnglish (US)
Article numbere0107133
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2014

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erythropoiesis
umbilical cord
Globins
Erythropoiesis
blood cells
Stem cells
Fetal Blood
stem cells
Blood
Transcription Factors
Stem Cells
transcription factors
Switches
Gene expression
Adult Stem Cells
Genes
genes
transcriptome
Transcriptome
Blood Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis. / Li, Biaoru; Ding, Lianghao; Yang, Chinrang; Kang, Baolin; Liu, Li; Story, Michael D.; Pace, Betty S.

In: PloS one, Vol. 9, No. 9, e0107133, 01.09.2014.

Research output: Contribution to journalArticle

Li, Biaoru ; Ding, Lianghao ; Yang, Chinrang ; Kang, Baolin ; Liu, Li ; Story, Michael D. ; Pace, Betty S. / Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis. In: PloS one. 2014 ; Vol. 9, No. 9.
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