Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and 29 in the mesoderm when analyzing FACS-purified cells derived from human embryonic stem cells. The mesodermal-enriched miR-483-3p was identified as an important regulator for the generation of mesodermal PDGFRA paraxial cells. Repression of its target PGAM1 significantly increased the number of PDGFRA cells. Furthermore, miR-483-3p, miR-199a-3p, and miR-214-3p might also have functions for the mesodermal progenitors. The endoderm-specific miR-489-3p and miR-1263 accelerated and increased endoderm differentiation upon overexpression. KLF4 was identified as a target of miR-1263. RNAi-mediated downregulation of KLF4 partially mimicked miR-1263 overexpression. Thus, the effects of this miRNA were mediated by facilitating differentiation through destabilization of pluripotency along with other not yet defined targets.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688239 | PMC |
http://dx.doi.org/10.1016/j.stemcr.2017.10.011 | DOI Listing |
Cell Rep
January 2025
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel. Electronic address:
During development, amniote vertebrate embryos transform from a flat sheet into a three-dimensional cylindrical form through ventral folding of the lateral sides of the sheet (the lateral plate [LP]) and their fusion in the ventral midline. Using a chick embryo slice system, we find that the flat stage is actually a poised balance of opposing dorsal and ventral elastic bending tensions. An intact extracellular matrix (ECM) is required for generating tension, as localized digestion of ECM dissipates tension, while removal of endoderm or ectoderm layers has no significant effect.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Gastrulation marks a pivotal stage in mammalian embryonic development, establishing the three germ layers and body axis through lineage diversification and morphogenetic movements. However, studying human gastrulating embryos is challenging due to limited access to early tissues. Here we show the use of spatial transcriptomics to analyse a fully intact Carnegie stage 7 human embryo at single-cell resolution, along with immunofluorescence validations in a second embryo.
View Article and Find Full Text PDFDevelopment
January 2025
Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.
Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over development: it is expressed at higher levels in the blastula compared to the gastrula suggesting a critical role prior to gastrulation. We find depletion of Nup107 affects the differentiation of the early germ layers leading to an expansion of the ectoderm at the expense of endoderm and mesoderm.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
The mechanism by which DNA-damage affects self-renewal and pluripotency remains unclear. DNA damage and repair mechanisms have been largely elucidated in mutated cancer cells or simple eukaryotes, making valid interpretations on early development difficult. Here we show the impact of ionizing irradiation on the maintenance and early differentiation of mouse embryonic stem cells (ESCs).
View Article and Find Full Text PDFStem Cell Reports
January 2025
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research at MIT, 500 Main St, Cambridge, MA 02142, USA. Electronic address:
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!