title: Histone deacetylases differentially regulate the proliferative phenotype of mouse bone marrow stromal and hematopoietic stem/progenitor cells.
abstract: Mouse bone marrow stromal stem/progenitor cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and Hematopoietic Stem and Progenitor Cells (HSPCs) with differential proliferative potentials were investigated for identifying epigenetic signals that can modulate their growth. In the present study, immunodepletion of granulo-monocytic (CD11b) and erythroid (Ter119) population yielded CD11b(-)/Ter119(-) cells, capable of differentiating into chondrogenic, osteogenic and adipogenic cells. Enrichment of the CD11b(+) population by positive selection of multipotent stem/progenitor marker (CD133) yielded CD11b(+)/CD133(+) cells, efficiently differentiated into hematopoietic lineages. Molecular characterization revealed the expression of BMSC and HSPC markers in CD11b(-)/Ter119(-) and CD11b(+)/CD133(+) sorted populations, respectively. Cell expansion studies depicted a higher growth rate and percentage of proliferating cells in G2/M phase of cell cycle in BMSCs (13.9±2.9%) as compared with HSPCs (5.8±0.8%). Analysis of the HDACs gene expression revealed a differential expression pattern in BMSCs and HSPCs that modulates the cell cycle genes. Trichostatin A (TSA)-mediated HDAC inhibition led to an increased level of AcH3 and AcH4 along with cyclins B1 and D2. Chromatin immunoprecipitation revealed alleviation of HDAC2 and HDAC3 binding by TSA on cyclins B1 and D2 promoter, thereby enhancing cell proliferation. This study identifies epigenetic modulation on the proliferative potential of BMSCs and HSPCs for stem cell transplantation therapies.
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India; Academy of Scientific & Innovative Research, 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Neha R
authors.initials: NR
authors.lastname: Dhoke
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India.
authors.forename: Evangelene
authors.initials: E
authors.lastname: Kalabathula
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India; Academy of Scientific & Innovative Research, 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Kaushik
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India; Academy of Scientific & Innovative Research, 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Ramasatyaveni
authors.initials: R
authors.lastname: Geesala
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India.
authors.forename: B
authors.initials: B
authors.lastname: Sravani
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 007, India; Academy of Scientific & Innovative Research, 2 Rafi Marg, New Delhi 110 001, India. Electronic address: amitavadas@iict.res.in.
authors.forename: Amitava
authors.initials: A
authors.lastname: Das
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001789:Blood Group Antigens / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice
chemical_list: D000071916:AC133 Antigen; D001789:Blood Group Antigens; D039481:CD11b Antigen; D056744:Cyclin B1; D056742:Cyclin D2; D006877:Hydroxamic Acids; C489122:TER-119 antigen, mouse; C012589:trichostatin A; D006655:Histone Deacetylases
keywords: BMSCs; Cyclin B1; Cyclin D2; HDAC2; HDAC3; HSPCs