Publication details

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

Authors

BAGHERPOOR Alireza Jian DOLEŽALOVÁ Dáša BÁRTA Tomáš KUČÍREK Martin SANI Soodabeh Abbasi EŠNER Milan BOSÁKOVÁ Michaela VINARSKÝ Vladimír PEŠKOVÁ Lucie HAMPL Aleš ŠTROS Michal

Year of publication 2017
Type Article in Periodical
Magazine / Source Stem Cells and Development
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1089/scd.2016.0274
Field Genetics and molecular biology
Keywords human embryonic stem cells; HMGB1; HMGB2; neuroectodermal cells; differentiation
Description 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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