Functional analyses of the polycomb‐group genes in sea lamprey embryos undergoing programmed DNA loss DOI Creative Commons

Cody Saraceno,

Vladimir A. Timoshevskiy, Jeramiah J. Smith

et al.

Journal of Experimental Zoology Part B Molecular and Developmental Evolution, Journal Year: 2023, Volume and Issue: 342(3), P. 260 - 270

Published: Oct. 30, 2023

Abstract During early development, sea lamprey embryos undergo programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost the cell. Previous studies indicated that many genes eliminated during PGR have mammalian homologs bound by polycomb repressive complex (PRC) embryonic stem cells. To test whether PRC components play role faithful germline‐specific sequences, we used combination CRISPR/Cas9 lightsheet microscopy to investigate impact gene knockouts on development progression through stages elimination. Analysis knockout for core PRC2 subunits EZH, SUZ12, EED show disruption all three results an increase micronucleus number, altered distribution micronuclei within embryos, volume mutant embryos. While upstream events not strongly impacted loss components, this study suggests plays later related condensation degradation. These findings also suggest other genes/epigenetic pathways may work parallel mediate chromatin structure, accessibility, ultimate DNA.

Language: Английский

The first two blastomeres contribute unequally to the human embryo DOI Creative Commons
Sergi Junyent, Maciej Meglicki, Roman Vetter

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2838 - 2854.e17

Published: May 1, 2024

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to 2-cell stage embryo. However, whether and how such asymmetries arise embryo is unclear. Here, we performed prospective tracing human embryos using live imaging, non-invasive cell labeling, computational predictions determine contribution each blastomere epiblast (body), hypoblast (yolk sac), trophectoderm (placenta). We show majority cells originate from only one observe three become internalized at 8-to-16-cell transition. Moreover, these are more frequently derived first divide stage. propose division dynamics a internalization bottleneck early establish asymmetry composition future body.

Language: Английский

Citations

29
Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts DOI Creative Commons
Effrosyni A. Chavli, Sjoerd J. Klaasen, Diane Van Opstal

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(6)

Published: Jan. 4, 2024

Aneuploidy, a deviation from the normal chromosome copy number, is common in human embryos and considered primary cause of implantation failure early pregnancy loss. Meiotic errors lead to uniformly abnormal karyotypes, while mitotic chromosomal mosaicism: presence cells with at least two different karyotypes within an embryo. Knowledge about mosaicism blastocysts mainly derives bulk DNA sequencing multicellular trophectoderm (TE) and/or inner cell mass (ICM) samples. However, this can only detect average net gain or loss above detection threshold 20-30%. To accurately assess mosaicism, we separated TE ICM 55 good quality surplus successfully applied single-cell whole genome (scKaryo-seq) on 1057 cells. Mosaicism involving numerical structural abnormalities was detected 82% embryos, where most affected less than 20% Structural abnormalities, potentially caused by replication stress damage, were observed 69% embryos. In conclusion, our findings indicated that prevalent good-quality blastocysts, these would likely be identified as current techniques used for preimplantation genetic testing aneuploidy (PGT-A).

Language: Английский

Citations

18
Why study human embryo development? DOI Creative Commons
Janet Rossant

Developmental Biology, Journal Year: 2024, Volume and Issue: 509, P. 43 - 50

Published: Feb. 5, 2024

Understanding the processes and mechanisms underlying early human embryo development has become an increasingly active important area of research. It potential for insights into clinical issues such as pregnancy loss, origins congenital anomalies developmental adult disease, well fundamental biology. Improved culture systems preimplantation embryos, combined with new tools single cell genomics live imaging, are providing similarities differences between mouse development. However, access to material is still restricted extended embryos regulatory ethical concerns. Stem cell-derived models different phases can potentially overcome these limitations provide a scalable source explore postimplantation stages To date, clearly incomplete replicas normal but future technological improvements be envisaged. The environment studies remains fully resolved.

Language: Английский

Citations

12
Shape of the first mitotic spindles impacts multinucleation in human embryos DOI Creative Commons
Yuki Ono, Hiromitsu Shirasawa, Kazumasa Takahashi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 25, 2024

Abstract During human embryonic development, early cleavage-stage embryos are more susceptible to errors. Studies have shown that many problems occur during the first mitosis, such as direct cleavage, chromosome segregation errors, and multinucleation. However, mechanisms whereby these errors mitosis in remain unknown. To clarify this aspect, present study, we image discarded living two-pronuclear stage zygotes using fluorescent labeling confocal microscopy without microinjection of DNA or mRNA investigate association between spindle shape nuclear abnormality mitosis. We observe mitotic spindles vary, low-aspect-ratio-shaped tend lead formation multiple nuclei at 2-cell stage. Moreover, defocusing poles spindles, which strongly associated with Additionally, show differences positions centrosomes cause Furthermore, multinuclei modified form mononuclei after second because occurrence pole is firmly reduced. Our study will contribute markedly research on cleavage embryos.

Language: Английский

Citations

8
Insights into embryonic chromosomal instability: mechanisms of DNA elimination during mammalian preimplantation development DOI Creative Commons
Jacqueline Budrewicz, Shawn L. Chavez

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 5, 2024

Mammalian preimplantation embryos often contend with aneuploidy that arose either by the inheritance of meiotic errors from gametes, or mitotic mis-segregation events occurred following fertilization. Regardless origin, mis-segregated chromosomes become encapsulated in micronuclei (MN) are spatially isolated main nucleus. Much our knowledge MN formation comes dividing somatic cells during tumorigenesis, but error-prone cleavage-stage early embryogenesis is fundamentally different. One unique aspect cellular fragmentation (CF), whereby small subcellular bodies pinch off embryonic blastomeres, frequently observed. CF has been detected both

Language: Английский

Citations

4
Quantifying DNA damage following light sheet and confocal imaging of the mammalian embryo DOI Creative Commons
Darren J. X. Chow, Erik P. Schartner, Stella Corsetti

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 5, 2024

Language: Английский

Citations

4
All-optical polarization-filtered subwavelength imaging in microwave regime via atom-based polarization holography DOI Creative Commons
Ziyao Lyu, Tao Dong, Yijie Du

et al.

Communications Physics, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 19, 2025

Language: Английский

Citations

0
Re-biopsy and modified biopsy in mosaic human embryos with simple segmental deletion DOI
Weizhou Wang, Bin Liu, Zhi-Ping Jin

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Background: There is a considerable proportion of false positive when the result preimplantation genetic testing for aneuploidy chromosomal mosaicism. To assess concordance among clinical trophectoderm biopsy, second and inner cell mass biopsy in mosaic human embryos with segmental deletion evaluate modified protocol. Methods: This retrospective study was included 102 pretested blastocysts, which were classified as mosaics one to two chromosomes affected, donated by 84 couples single, high-volume fertility center Beijing China. Re-biopsy taken from symmetrical sites near each embryo. Samples prepared protocol, isolated portions into single cells, cells normal morphology collected debris removed. samples analyzed next-generation sequencing. Main outcome measures between blastocyst, mosaicism Results: Only six (6.4%) 94 presented concordant aberrations, four (4.2%) de novo abnormalities, (89.4%) did not show any abnormalities. For trophectodermsamples, 64 (67.4%) 95 biopsies 78 (80.4%) 97 or duplication. The protocol associated fewer abnormalities (19.6% versus 32.6%; odds ratio: 0.503, 95% confidence interval: 0.26 0.973) (10.3% 23.2%; 0.381, 0.17 0.857) compared biopsy. Conclusions: A embryo simple extremely low predictive Removal could reduce incidence mosaics. Clinical trial registration:not applicable.

Language: Английский

Citations

0
Functions and mechanisms of eukaryotic RNA-guided programmed DNA elimination DOI Creative Commons
Bozhidar‐Adrian Stefanov, Mariusz Nowacki

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 53(02), P. 473 - 485

Published: April 1, 2025

Many eukaryotic organisms, from ciliates to mammals, employ programmed DNA elimination during their postmeiotic reproduction. The process removes specific regions the somatic and has broad functions, including irreversible silencing of genes, sex determination, genome protection transposable elements or integrating viruses. Multiple mechanisms have evolved that explain sequence selectivity process. In some cases, eliminated sequences lack centromeres are flanked by conserved motifs specifically recognized cleaved designated nucleases. Upon cleavage, all fragments lost following mitosis. Alternatively, can be destined for complementary small RNAs (sRNAs) as in ciliates. These sRNAs enable a PIWI-mediated recruitment chromatin remodelers, followed up precise positioning cleavage complex formed transposase like PiggyBac Tc1. Here, we review known molecular interplay cellular machinery is involved sRNA-guided excision, additionally, highlight prominent knowledge gaps. We focus on modes through which localization complex, how nuclease activity controlled prevent off-target cleavage. A mechanistic understanding this could development novel editing tools.

Language: Английский

Citations

0
Cell competition eliminates aneuploid human pluripotent stem cells DOI Creative Commons
Amanda Ya, Chenhui Deng, Kristina Godek

et al.

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102506 - 102506

Published: May 1, 2025

Citations

0