2. Academic Validation
  3. Binary Colloidal Crystals Promote Cardiac Differentiation of Human Pluripotent Stem Cells via Nuclear Accumulation of SETDB1

Binary Colloidal Crystals Promote Cardiac Differentiation of Human Pluripotent Stem Cells via Nuclear Accumulation of SETDB1

  • ACS Nano. 2023 Jan 19. doi: 10.1021/acsnano.3c00009.
Yongping Lin 1 2,  Feng Zhang 1,  Shaojie Chen 1,  Xiyu Zhu 3,  Jincheng Jiao 4,  Yike Zhang 1,  Zhaomin Li 1,  Jiao Lin 5,  Biao Ma 4,  Minglong Chen 1 2 6,  Peng-Yuan Wang 7,  Chang Cui 1
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing210000, Jiangsu, China.
  • 2 Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou225300, Jiangsu, China.
  • 3 Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing210000, China.
  • 4 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing210000, Jiangsu, China.
  • 5 Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen518000, Guangdong, China.
  • 6 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing210000, Jiangsu, China.
  • 7 Oujiang Laboratory; Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou325000, Zhejiang, China.
PMID: 36655945 DOI: 10.1021/acsnano.3c00009
Abstract

Biophysical cues can facilitate the cardiac differentiation of human pluripotent stem cells (hPSCs), yet the mechanism is far from established. One of the binary colloidal crystals, composed of 5 μm Si and 400 nm poly(methyl methacrylate) particles named 5PM, has been applied as a substrate for hPSCs cultivation and cardiac differentiation. In this study, cell nucleus, Cytoskeleton, and epigenetic states of human induced pluripotent stem cells on the 5PM were analyzed using atomic force microscopy, Molecular Biology assays, and the assay for transposase-accessible chromatin Sequencing (ATAC-seq). Cells were more spherical with stiffer cell nuclei on the 5PM compared to the flat control. ATAC-seq revealed that chromatin accessibility decreased on the 5PM, caused by the increased entry of histone lysine methyltransferase SETDB1 into the cell nuclei and the amplified level of histone H3K9me3 modification. Reducing Cytoskeleton tension using a ROCK Inhibitor attenuated the nuclear accumulation of SETDB1 on the 5PM, indicating that the effect is cytoskeleton-dependent. In addition, the knockdown of SETDB1 reversed the promotive effects of the 5PM on cardiac differentiation, demonstrating that biophysical cue-induced cytoskeletal tension, cell nucleus deformation, and then SETDB1 accumulation are critical outside-in signal transformations in cardiac differentiation. Human embryonic stem cells showed similar results, indicating that the biophysical impact of the 5PM surfaces on cardiac differentiation could be universal. These findings contribute to our understanding of material-assistant hPSC differentiation, which benefits materiobiology and stem cell bioengineering.

Keywords

biophysical cues; epigenetics; histone modulation; pluripotent stem cell; topography.

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