The nuclear transporter importin 13 is critical for cell survival during embryonic stem cell differentiation
| Autor: | Shadma Fatima, Kylie M. Wagstaff, Julia C. Young, Sue Mei Lim, David A. Jans, Jose M. Polo |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Brachyury Mesoderm Cell Survival Biophysics Apoptosis Ectoderm Importin Karyopherins Biology Biochemistry Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Proliferation Marker Molecular Biology Embryoid Bodies Embryonic Stem Cells Cell Proliferation Cell Differentiation Cell Biology Embryonic stem cell Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Nuclear transport Endoderm Octamer Transcription Factor-3 |
| Zdroj: | Biochemical and Biophysical Research Communications. 534:141-148 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.11.099 |
| Popis: | Nuclear transporter Importin (Imp, Ipo) 13 is known to transport various mammalian cargoes into/out of the nucleus, but its role in directing cell-fate is unclear. Here we examine the role of Imp13 in the maintenance of pluripotency and differentiation of embryonic stem cells (ESCs) for the first time, using an embryonic body (EB)-based model. When induced to differentiate, Ipo13-/- ESCs displayed slow proliferation, reduced EB size, and lower expression of the proliferation marker KI67, concomitant with an increase in the number of TUNEL+ nuclei compared to wildtype ESCs. At days 5 and 10 of differentiation, Ipo13-/- EBs also showed enhanced loss of the pluripotency transcript OCT3/4, and barely detectable clusters of OCT3/4 positive cells. Day 5 Ipo13-/- EBs further exhibited reduced levels of the mesodermal markers Brachyury and Mixl1, correlating with reduced numbers of haemoglobinised cells generated. Our findings suggest that Imp13 is critical to ESC survival as well as early post-gastrulation differentiation. |
| Databáze: | OpenAIRE |
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