Localization of human chorionic gonadotropin and placental lactogen by immunogold labeling for electron microscopy: Technique and limitations

Morrish, Donald W.; Marusyk, Halyna

doi:10.1002/(sici)1097-0029(19970701/15)38:1/2<176::aid-jemt18>3.0.co;2-m

Cited by 8 publications

(1 citation statement)

References 43 publications

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“…Despite the STB being one large cytoplasm where molecules can freely mix by diffusion, it has long been suggested to contain distinct cytoplasmic zones that specialize in different functions (Benirschke et al, 2012; Burgos and Rodríguez, 1966; Burton, 1990). For example, STB cytoplasmic regions adjacent to the fetal vasculature dramatically thin to facilitate diffusional exchange and express angiogenic promoting proteins while regions where hormones are produced will exhibit dense packing of cytoplasmic organelles and express hormone and protein trafficking molecules (Baczyk et al, 2004; Beck et al, 1986; Burton and Jauniaux, 1995; Clark et al, 1998; Hempstock et al, 2003; Jauniaux et al, 2003; Khaliq et al, 2009; Morrish and Marusyk, 1997; Mouzon, 1997; Sharkey et al, 1993). One potential mechanism for creating these distinct cytoplasmic zones is nuclear specialization, whereby individual nucleus identities might be spatially localized to different cytoplasmic regions, as has been demonstrated for nuclei in syncytial muscle fibers (Kim et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing

Keenen,

Yang,

Liang

et al. 2024

Preprint

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The outer surface of chorionic villi in the human placenta consists of a single multinucleated cell called the syncytiotrophoblast (STB). The unique cellular ultrastructure of the STB presents challenges in deciphering its gene expression signature at the single-cell level, as the STB contains billions of nuclei in a single cell. There are many gaps in understanding the molecular mechanisms and developmental trajectories involved in STB formation and differentiation. To identify the underlying control of the STB, we performed comparative single nucleus (SN) and single cell (SC) RNA sequencing on placental tissue and tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture the STB population from both tissue and TOs. Differential gene expression and pseudotime analysis of TO-derived STB identified three distinct nuclear subtypes reminiscent of those recently identifiedin vivo. These included a juvenile nuclear population that exhibited both CTB and STB marker expression, a population enriched in genes involved in oxygen sensing, and a fully differentiated subtype. Notably, suspension culture conditions of TOs that restore the native orientation of the STB (STBout) showed elevated expression of canonical STB markers and pregnancy hormones, along with a greater proportion of the terminally differentiated mature STB subtype, compared to those cultivated with an inverted STB polarity (STBin). Gene regulatory analysis identified novel markers of STB differentiation conserved in tissue and TOs, including the chromatin remodeler RYBP, that exhibited STB-specific RNA and protein expression. Finally, we compared STB gene expression signatures amongst first trimester tissue, full-term tissue, and TOs, identifying many commonalities but also notable variability across each sample type. This indicates that STB gene expression is responsive to its environmental context. Our findings emphasize the utility of TOs to accurately model STB differentiation and the distinct nuclear subtypes observedin vivo, offering a versatile platform for unraveling the molecular mechanisms governing STB functions in placental biology and disease.

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