scholarly journals Dynamic erasure of X chromosome upregulation during iPSC reprogramming and in the inner cell mass

2020 ◽  
Author(s):  
D Chandel ◽  
C H Naik ◽  
S Gayen

SummaryRecent studies have provided substantial evidence supporting Ohno’s hypothesis that upregulation of active X chromosome genes balances the dosage relative to autosomal genes. Here, we found the evidence for erasure of active X-chromosome upregulation upon reactivation of inactive X in female cells during iPSC reprogramming and in the inner cell mass of mouse blastocyst. Moreover, our analysis revealed that the kinetics of erasure of X upregulation is tightly linked with the dynamics of X reactivation.Abstract Figure

Development ◽  
1987 ◽  
Vol 100 (2) ◽  
pp. 325-332
Author(s):  
C.L. Garbutt ◽  
M.H. Johnson ◽  
M.A. George

Aggregate 8-cell embryos were constructed from four 2/8 pairs of blastomeres, one of which was marked with a short-term cell lineage marker and was also either 4 h older (derived from an early-dividing 4-cell) or 4 h younger (derived from a late-dividing 4-cell) than the other three pairs. The aggregate embryos were cultured to the 16-cell stage, at which time a second marker was used to label the outside cell population. The embryos were then disaggregated and each cell was examined to determine its labelling pattern. From this analysis, we calculated the relative contributions to the inside cell population of the 16-cell embryo of older and younger cells. Older cells were found to contribute preferentially. However, if the construction of the aggregate 8-cell embryo was delayed until each of the contributing 2/8 cell pairs had undergone intercellular flattening and then had been exposed to medium low in calcium to reverse this flattening immediately prior to aggregation, the advantage possessed by the older cells was lost. These results support the suggestion that older cells derived from early-dividing 4-cell blastomeres contribute preferentially to the inner cell mass as a result of being early-flattening cells.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1016 ◽  
Author(s):  
Bo Yu ◽  
Helena T. A. van Tol ◽  
Tom A.E. Stout ◽  
Bernard A. J. Roelen

X-chromosome inactivation (XCI) is a developmental process that aims to equalize the dosage of X-linked gene products between XY males and XX females in eutherian mammals. In female mouse embryos, paternal XCI is initiated at the 4-cell stage; however, the X chromosome is reactivated in the inner cell mass cells of blastocysts, and random XCI is subsequently initiated in epiblast cells. However, recent findings show that the patterns of XCI are not conserved among mammals. In this study, we used quantitative RT-PCR and RNA in situ hybridization combined with immunofluorescence to investigate the pattern of XCI during bovine embryo development. Expression of XIST (X-inactive specific transcript) RNA was significantly upregulated at the morula stage. For the first time, we demonstrate that XIST accumulation in bovine embryos starts in nuclei of female morulae, but its colocalization with histone H3 lysine 27 trimethylation was first detected in day 7 blastocysts. Both in the inner cell mass and in putative epiblast precursors, we observed a proportion of cells with XIST RNA and H3K27me3 colocalization. Surprisingly, the onset of XCI did not lead to a global downregulation of X-linked genes, even in day 9 blastocysts. Together, our findings confirm that diverse patterns of XCI initiation exist among developing mammalian embryos.


2017 ◽  
Vol 41 (5) ◽  
pp. 496-510.e5 ◽  
Author(s):  
Minjung Kang ◽  
Vidur Garg ◽  
Anna-Katerina Hadjantonakis

Development ◽  
1972 ◽  
Vol 28 (2) ◽  
pp. 279-312
Author(s):  
R. L. Gardner ◽  
M. H. Johnson

1. Inner cell mass (ICM) and trophoblast were isolated from 3½-day post-coitum mouse blastocysts by microsurgery. 2. Trophoblastic fragments formed vesicles in culture but did not aggregate with other such fragments. They proved as effective as intact blastocysts in inducing decidua in recipient uteri, but thereafter failed to proliferate. 3. Isolated ICMs remained as solid balls of cells that readily aggregated in pairs or groups in culture but failed to induce implantation changes in receptive uteri. 4. Possible explanations for the failure of isolated trophoblast to proliferate after implantation are discussed. It is argued that presence of ICM tissue is necessary for trophoblast proliferation, and suggested that the ICM exerts its effect by controlling development of the ectoplacental cone.


Development ◽  
1982 ◽  
Vol 67 (1) ◽  
pp. 127-135
Author(s):  
Mary I. Harper ◽  
Mandy Fosten ◽  
Marilyn Monk

The preferential expression of the maternal X chromosome seen in certain extraembryonic membranes of the mouse was studied by investigating the tissues from which these membranes are derived during early development. The electrophoretic variant of the X-coded enzyme PGK-1 (phosphoglycerate kinase) was used to distinguish the expression of the maternal from the paternal X chromosome in heterozygous females. Both the extraembryonic ectoderm and primary endoderm of 6½-day female egg cylinders gave almost exclusive expression of the maternal form of the enzyme whereas the epiblast gave near equal expression of the two parental alleles. No paternal PGK-1 band could be detected in samples of pooled 3½-day blastocysts, but after 3 or 4 days of culture in vitro a faint paternal band was seen in the resultant outgrowths. The activity of the maternal band in these latter samples had increased greatly from that of the blastocysts, consistent with preferential expression of the maternal Pgk-1 allele in the trophoblastic cells of the outgrowths, while both alleles are expressed in inner-cell-mass cells. The results strongly support the idea that non-random X-chromosome expression is due to preferential paternal X inactivation in trophectoderm (from which extraembryonic ectoderm is derived) and in primary endoderm, and not to cell selection.


Stem Cells ◽  
2013 ◽  
Vol 31 (9) ◽  
pp. 1932-1941 ◽  
Author(s):  
Jérôme Artus ◽  
Minjung Kang ◽  
Michel Cohen-Tannoudji ◽  
Anna-Katerina Hadjantonakis

2012 ◽  
Vol 287 (39) ◽  
pp. 33094-33103 ◽  
Author(s):  
Martin B. Lee ◽  
Megan Kooistra ◽  
Baohua Zhang ◽  
Sandy Slow ◽  
Amanda L. Fortier ◽  
...  

1990 ◽  
Vol 10 (9) ◽  
pp. 4987-4989 ◽  
Author(s):  
J Singer-Sam ◽  
M Grant ◽  
J M LeBon ◽  
K Okuyama ◽  
V Chapman ◽  
...  

A HpaII-PCR assay was used to study DNA methylation in individual mouse embryos. It was found that HpaII site H-7 in the CpG island of the X-chromosome-linked Pgk-1 gene is less than or equal to 10% methylated in oocytes and male embryos but becomes 40% methylated in female embryos at 6.5 days; about the time of X-chromosome inactivation of the inner cell mass.


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