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Epigenetic and molecular signatures of cord blood CD 34 + cells treated with histone deacetylase inhibitors
Author(s) -
Gajzer D.,
Ross J.,
Winder L.,
Navada S.,
Zhang W.,
Silverman L.,
Chaurasia P.
Publication year - 2016
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12303
Subject(s) - histone deacetylase , epigenetics , biology , haematopoiesis , trichostatin a , progenitor cell , microbiology and biotechnology , chromatin , cancer research , reprogramming , stem cell , erythropoiesis , histone , genetics , medicine , cell , gene , anemia
Background and Objectives Epigenetic modifications tightly regulate the gene expression and cellular function of haematopoietic stem cells. Histone deacetylase inhibitors ( HDACI s) alter the gene expression profile of cord blood ( CB ) CD 34 + cells by controlling the genes involved in chromatin modification, thereby influencing the self‐renewal, maintenance and expansion of haematopoietic stem and progenitor cells ( HSPC s). Materials and Methods The class I and II HDACI s, valproic acid and scriptaid, were utilized to expand CB ‐ CD 34 + cells ex vivo. The gene profiling was performed on HSPC using Illumina microarray, Gene GO MetaCore ™ and Ingenuity pathway analyses. The molecular analyses were performed using Q‐ PCR and Western blotting. Results Each HDACI treatment of CB ‐ CD 34 + cells created unique epigenetic and molecular signatures that governed chromatin modification required for cellular and functional behaviour of stem cells. Gene GO MetaCore ™ and Ingenuity pathway analyses established the molecular understanding of epigenetically regulated HSPC s in the presence of scriptaid and VPA that revealed different network(s) of potential regulators during erythropoiesis. VPA induced transcriptional activation of the glucocorticoid receptor ( GCR ) and an increase in the intracellular signalling of signal transducers and activators of transcription ( STAT ) required during stress erythropoiesis. Canonical Wnt signalling and many epigenetically regulated chromatin remodellers were significantly influenced so as to establish maintenance and regulation of HSPC . Conclusion Treatment with Individual HDACI s has demonstrated significantly unique epigenetic and molecular signatures of CB ‐ HSPC . This study identifies potential key regulators of HSPC and gives insights into the clinically important processes of HSPC expansion and haematopoietic lineage development for transplantation purposes.