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Properties of Human Embryonic Stem Cells and Their Differentiated Derivatives Depend on Nonhistone DNA-Binding HMGB1 and HMGB2 Proteins

AJ. Bagherpoor, D. Dolezalova, T. Barta, M. Kučírek, SA. Sani, M. Ešner, M. Kunova Bosakova, V. Vinarský, L. Peskova, A. Hampl, M. Štros,

. 2017 ; 26 (5) : 328-340. [pub] 20161223

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17031281

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.

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$a HMGB1 and HMGB2 proteins have been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It is unknown whether they are involved in regulating the typical functions of pluripotent human embryonic stem cells (hESCs) and/or those of the differentiated derivatives of hESCs. Using inducible, stably transfected hESCs capable of shRNA-mediated knockdown of HMGB1 and HMGB2, we provide evidence that downregulation of HMGB1 and/or HMGB2 in undifferentiated hESCs does not affect the stemness of cells and induces only minor changes to the proliferation rate, cell-cycle profile, and apoptosis. After differentiation is induced, however, the downregulation of those proteins has important effects on proliferation, apoptosis, telomerase activity, and the efficiency of differentiation toward the neuroectodermal lineage. Furthermore, those processes are affected only when one, but not both, of the two proteins is downregulated; the knockdown of both HMGB1 and HMGB2 results in a normal phenotype. Those results advance our knowledge of regulation of hESC and human neuroectodermal cell differentiation and illustrate the distinct roles of HMGB1 and HMGB2 during early human development.
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$a Dolezalova, Dasa $u 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
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$a Barta, Tomas $u 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic . 3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
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$a Kučírek, Martin $u 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
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$a Sani, Soodabeh Abbasi $u 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
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$a Ešner, Milan $u 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
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$a Kunova Bosakova, Michaela $u 4 Department of Biology, Faculty of Medicine, Masaryk University , Brno, Czech Republic .
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$a Vinarský, Vladimír $u 3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
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$a Peskova, Lucie $u 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic .
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$a Hampl, Aleš $u 2 Department of Histology and Embryology, Masaryk University , Brno, Czech Republic . 3 International Clinical Research Center, St. Anne's University Hospital , Brno, Czech Republic .
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$a Štros, Michal $u 1 Laboratory of Analysis of Chromosomal Proteins, Institute of Biophysics , Academy of Sciences of the Czech Republic, Brno, Czech Republic .
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