title: Properties of Human Embryonic Stem Cells and Their Differentiated Derivatives Depend on Nonhistone DNA-Binding HMGB1 and HMGB2 Proteins.
abstract: HMGB1 and HMGB2 proteins have been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It is unknown whether they are involved in regulating the typical functions of pluripotent human embryonic stem cells (hESCs) and/or those of the differentiated derivatives of hESCs. Using inducible, stably transfected hESCs capable of shRNA-mediated knockdown of HMGB1 and HMGB2, we provide evidence that downregulation of HMGB1 and/or HMGB2 in undifferentiated hESCs does not affect the stemness of cells and induces only minor changes to the proliferation rate, cell-cycle profile, and apoptosis. After differentiation is induced, however, the downregulation of those proteins has important effects on proliferation, apoptosis, telomerase activity, and the efficiency of differentiation toward the neuroectodermal lineage. Furthermore, those processes are affected only when one, but not both, of the two proteins is downregulated; the knockdown of both HMGB1 and HMGB2 results in a normal phenotype. Those results advance our knowledge of regulation of hESC and human neuroectodermal cell differentiation and illustrate the distinct roles of HMGB1 and HMGB2 during early human development.
authors.affiliation: 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
authors.forename: Alireza Jian
authors.initials: AJ
authors.lastname: Bagherpoor
authors.affiliation: 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
authors.forename: Dasa
authors.initials: D
authors.lastname: Dolezalova
authors.affiliation: 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .|3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
authors.forename: Tomas
authors.initials: T
authors.lastname: Barta
authors.affiliation: 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
authors.forename: Martin
authors.initials: M
authors.lastname: Kučírek
authors.affiliation: 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
authors.forename: Soodabeh Abbasi
authors.initials: SA
authors.lastname: Sani
authors.affiliation: 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
authors.forename: Milan
authors.initials: M
authors.lastname: Ešner
authors.affiliation: 4 Department of Biology, Faculty of Medicine, Masaryk University , Brno, Czech Republic .
authors.forename: Michaela
authors.initials: M
authors.lastname: Kunova Bosakova
authors.affiliation: 3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
authors.forename: Vladimír
authors.initials: V
authors.lastname: Vinarský
authors.affiliation: 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
authors.forename: Lucie
authors.initials: L
authors.lastname: Peskova
authors.affiliation: 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .|3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
authors.forename: Aleš
authors.initials: A
authors.lastname: Hampl
authors.affiliation: 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
authors.forename: Michal
authors.initials: M
authors.lastname: Štros
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D024243:HMGB1 Protein / Q000378:metabolism*; D024261:HMGB2 Protein / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D054258:Neural Plate / Q000166:cytology; D019098:Telomerase / Q000378:metabolism; D014162:Transfection
chemical_list: D024243:HMGB1 Protein; D024261:HMGB2 Protein; D006657:Histones; D019098:Telomerase
keywords: HMGB1; HMGB2; differentiation; human embryonic stem cells; neuroectodermal cells