Biology subjects

Shahbazi, M. N.

Publications and source records attributed to Shahbazi, M. N..

3 recordsLinked to original sources

bioRxiv2026

Dynein-dependent positioning of multiple organelles regulates adaptive gene expression during oxidative stress

Cells respond to environmental insults through well-characterized changes to their transcriptome and proteome. The contribution that reorganization of intracellular architecture makes to the adaptive stress response is much less understood. Here, we reveal a conserved spatial response to oxidative stress in which the microtubule motor dynein enhances perinuclear clustering of multiple membrane-bound organelles. These events are triggered by reactive oxygen species and protein kinase C and occur without increased association of dynein with its activator dynactin, pointing to a non-canonical mechanism for stimulating retrograde transport. Using a chemically-inducible system for dispersing individual organelles, we show that perinuclear localization of multiple compartments potentiates oxidative stress-induced gene expression, with distinct genes depending on inputs from either combinations of organelles or individual compartments. Together, these findings implicate positioning of multiple membrane-bound compartments in gene expression regulation and identify coordinated organelle trafficking by dynein as an additional regulatory layer in the cellular stress response.

cell biology↗

bioRxiv2025

A blastocyst-derived in vitro model of the human chorion

The placenta supports the foetus by mediating nutrient and gas exchange, hormone production, and immune protection. Yet, human placental biology remains poorly understood due to limited in vitro models. The foetal part of the placenta, the chorion, consists of a trophoblast-derived layer and a mesenchymal zone containing extraembryonic mesoderm cells. Here, we show that human blastocysts can give rise to both trophoblast organoids and extraembryonic mesoderm cells under the same culture conditions. Trophoblast organoids originate from both outer trophoblast cells and inner cells of the blastocyst, while extraembryonic mesoderm cells derive exclusively from inner cells. These organoids recapitulate the cellular composition, morphology, and function of the in vivo trophoblast. Moreover, given the high rate of aneuploidy at the blastocyst stage, aneuploid trophoblast organoids can be readily generated. These models reflect the trophoblasts unique ability to tolerate aneuploidy and offer a valuable platform to study human placental development and pathophysiology.

developmental biology↗

bioRxiv2020

Mechanism of cell polarisation and first lineage segregation in the human embryo

The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac1-3. The mechanism underlying this cell fate segregation has been extensively studied in the mouse embryo4,5. However, when and how it takes place in the human embryo remains unclear. Here, using time-lapse imaging and 325 surplus human embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in human embryogenesis. We show that the first lineage segregation of the human embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse embryos6. Finally, we show that, in contrast to the mouse embryo, the key extra-embryonic determinant GATA37,8 is expressed not only in extra-embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the human embryo.

developmental biology↗