Biology subjects

Paloviita, P.

Publications and source records attributed to Paloviita, P..

3 recordsLinked to original sources

bioRxiv2026

Hsa-miR-92a-3p regulates cell-cycle and signaling programs during human extra-embryonic lineage commitment

MicroRNA (miRNA) levels increase during human embryonic genome activation (EGA) and have been implicated in the first lineage decisions. Re-analyzing single-cell and bulk small RNA-seq (sRNA-seq) from human and mouse embryos, together with new sRNA-seq of naive human embryonic stem cells (hESCs) differentiated into hypoblast-like cells (HLCs) and extra-embryonic mesoderm (EXM)-like cells (EXMCs), we identify hsa-miR-92a-3p as highly expressed from oocyte to morula stage and dynamically regulated during HLC and EXMC formation. Functional inhibition of hsa-miR-92a-3p delays RACL (HLC/EXMC) differentiation, maintains epiblast-like and promotes trophectoderm (TE)-like transcriptional features, and reduces hypoblast and EXM marker acquisition. Transcriptome analyses revealed derepression of hsa-miR-92a-3p targets, including FGF2, and shifts in developmental and cell-cycle programs. The patterns of FGF protein stainings and flow cytometry-based cell-cycle analysis further implicate these pathways in RACL differentiation. Our findings position hsa-miR-92a-3p as a central regulator coordinating signaling and cell-cycle cues during extra embryonic lineage progression.

developmental biology↗

bioRxiv2025

Integrated transcriptomic analysis reveals a metabolically quiescent state and gene expression networks related to intermediate and mature human 8-cell stage embryo resembling cells in vitro

Human early development is challenging to study due to limited samples and cell numbers. The emergence of 8-cell stage embryo-like cells (8CLCs) offers new opportunities to understand embryonic genome activation (EGA) in humans. Our research compares and characterizes 8CLCs from various stem cell-based systems to determine how well these models reflect human early embryonic development. Using single-cell RNA sequencing (scRNA-seq) datasets from multiple studies, we integrated data to identify key gene co-expression modules, transposable element (TE) expression, and biological processes recapitulated in 8CLCs. We identified both mature and intermediate 8CLCs, with the Yoshihara and Mazid datasets best representing 8-cell stage embryos. 8CLCs show quiescence in energy and RNA metabolism, regulation of RNA splicing, and ribosome biogenesis, mirroring human 8-cell stage embryos. Our findings underscore the importance of distinguishing mature 8CLCs from partially reprogrammed cell states to improve their use as models for human EGA, in vitro.

developmental biology↗

bioRxiv2019

DUX4 regulates oocyte to embryo transition in human

During the human oocyte-to-embryo transition, the fertilized oocyte undergoes final maturation and the embryo genome is gradually activated during the first three cell divisions. How this transition is coordinated in humans is largely unknown. We show that the double homeodomain transcription factor DUX4 contributes to this transition. DUX4 knockdown in human zygotes caused insufficient transcriptome reprogramming as observed three days after fertilization. Induced DUX4 expression in human embryonic stem cells activated transcription of thousands of newly identified bi-directional transcripts, including putative enhancers for embryonic genome activation genes such as LEUTX. DUX4 protein interacted with transcriptional modifiers that are known to couple enhancers and promoters. Taken together, our results reveal that DUX4 is a pioneer regulating oocyte-to-embryo transition in human through activation of intergenic genome, especially enhancers, and hence setting the stage for early human embryo development.

developmental biology↗