Developmental potential of aneuploid human embryos cultured beyond implantation

Shahbazi, Marta; Wang, Tianren; Tao, Xin; Weatherbee, Bailey A. T.; Sun, Li; Zhan, Yiping; Keller, Laura; Smith, Gary D.; Pellicer, A.; Scott, Richard T.; Seli, Emre; Zernicka‐Goetz, Magdalena

doi:10.1038/s41467-020-17764-7

Cited by 79 publications

(61 citation statements)

References 56 publications

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“…In contrast to reports on widespread aneuploidy in pre-implantation human embryos 26–28 , we observed no early SVs or CNVs in any patients studied. This may suggest that aneuploid cells are purified from the lineages constituting the embryo proper, either through cell death or allocation to extraembryonic lineages.…”

Section: Resultscontrasting

confidence: 99%

Extensive phylogenies of human development reveal variable embryonic patterns

Coorens

Moore

et al. 2020

Preprint

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Starting from the zygote, all cells in the developing and adult human body continuously acquire mutations. A mutation shared between two different cells implies a shared progenitor cell and can thus be used as a naturally occurring marker for lineage tracing. Here, we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissected samples from multiple organs. Early embryonic progenitor cells inferred from the phylogenies often contribute in different proportions to the adult body and the extent of this asymmetry is variable between individuals, with ratios between the first two reconstructed cells ranging from 56:44 to 92:8. Asymmetries also pervade subsequent cell generations and can differ between tissues in the same individual. The phylogenies also resolve the spatial embryonic origins and patterning of tissues, revealing a spatial effect in the development of the human brain. Supplemented by data on eleven men, we timed the split between soma and germline, with the earliest observed segregation occurring at the first cell divisions. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.

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Section: Resultscontrasting

confidence: 99%

Extensive phylogenies of human development reveal variable embryonic patterns

Coorens

Moore

et al. 2020

Preprint

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“…It is important to note that we observe very high transcriptome similarity between hPSC-TS and placenta-derived TS cells ( Fig. 5 , A – C ), and conversion of primed hPSCs to TS cells using our approach has been independently replicated ( 40 ).…”

Section: Discussionmentioning

confidence: 73%

“…In the time since our results were reported in preprint form ( 39 ), our approach for generation of TS cells from hPSCs has been independently confirmed; Shahbazi et al . used our protocol to generate hPSC-TS cells from hESCs overexpressing an E-Cadherin-GFP fusion ( 40 ). Our results are also consistent with other recent work that has demonstrated derivation of TS cells from hPSCs, although using different differentiation protocols and in the absence of BMP treatment ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Two distinct trophectoderm lineage stem cells from human pluripotent stem cells

Mischler

Karakis

Mahinthakumar

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Such mosaic human embryos can still develop to term, as the aneuploid cells are often eliminated from the early embryo by mechanisms that are only poorly understood [ 4 ]. In contrast, meiotic aneuploidy affects the entire embryo, and most fully aneuploid embryos cannot develop to term [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Aneuploidy in human eggs: contributions of the meiotic spindle

Thomas

Cavazza

Schuh

2021

Biochemical Society Transactions

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Human eggs frequently contain an incorrect number of chromosomes, a condition termed aneuploidy. Aneuploidy affects ∼10–25% of eggs in women in their early 30s, and more than 50% of eggs from women over 40. Most aneuploid eggs cannot develop to term upon fertilization, making aneuploidy in eggs a leading cause of miscarriages and infertility. The cellular origins of aneuploidy in human eggs are incompletely understood. Aneuploidy arises from chromosome segregation errors during the two meiotic divisions of the oocyte, the progenitor cell of the egg. Chromosome segregation is driven by a microtubule spindle, which captures and separates the paired chromosomes during meiosis I, and sister chromatids during meiosis II. Recent studies reveal that defects in the organization of the acentrosomal meiotic spindle contribute to human egg aneuploidy. The microtubules of the human oocyte spindle are very frequently incorrectly attached to meiotic kinetochores, the multi-protein complexes on chromosomes to which microtubules bind. Multiple features of human oocyte spindles favour incorrect attachments. These include spindle instability and many age-related changes in chromosome and kinetochore architecture. Here, we review how the unusual spindle assembly mechanism in human oocytes contributes to the remarkably high levels of aneuploidy in young human eggs, and how age-related changes in chromosome and kinetochore architecture cause aneuploidy levels to rise even higher as women approach their forties.

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Developmental potential of aneuploid human embryos cultured beyond implantation

Cited by 79 publications

References 56 publications

Extensive phylogenies of human development reveal variable embryonic patterns

Extensive phylogenies of human development reveal variable embryonic patterns

Two distinct trophectoderm lineage stem cells from human pluripotent stem cells

Aneuploidy in human eggs: contributions of the meiotic spindle

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