Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development

Function of the 26S proteasome, a proteolytic organelle directed at proteins targeted for turnover by polyubiquitination, in preimplantation embryos is unclear. But it is well known to play a role in regulating meiosis. This paper reports the distribution of the proteasome and assessment of its functional importance in preimplantation development. Embryos from superovulated mice were either paraformaldehyde fixed for immunolabelling with a rabbit polyclonal antibody against the 20S proteasome core or cultured in KSOM medium with and without reversible (MG132) or irreversible (β-lactone) proteasomal inhibitors. Morphology, cell number, apoptosis and proteolysis were measured. Although diffuse throughout embryonic cytoplasm, there were distinct proteasomal concentrations in pronuclei, nuclei and cortical cytoplasm. When β-lactone was used to block blastocyst proteasomal proteolysis, ~25% of protein degradation was found to be proteasome-specific. Treatment of 2-cell embryos for more than 3 h with MG132 blocked blastocyst formation completely, even after washout, whilst both inhibitors reduced cell proliferation over the ensuing 48 h. Two hours exposure to MG132 tripled the proportion of apoptotic cells in expanded blastocysts 96 h post hCG. The nuclear concentration of proteasomes suggests a particular role in nuclear protein degradation possibly including the timed destruction of cell-cycle regulators and anti-apoptotic factors. This is supported by the loss-of-function studies which show that cell proliferation as well as morphogenesis require proteasomal activity at the late 2-cell stage and that without it apoptosis is dramatically increased. The mechanisms involved in the activation of apoptosis as a result of proteasomal inhibition in the early embryo are unknown but may include JNK signalling although this is controversial. More intriguing however is the identity of the proteasomal targets in the 2-cell embryo that must be degraded to permit continued morphogenesis.

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A species-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for preimplantation development

10.1101/2021.03.24.436683 ◽

2021 ◽

Author(s):

Andrew J Modzelewski ◽

Wanqing Shao ◽

Jingqi Chen ◽

Angus Lee ◽

Xin Qi ◽

...

Keyword(s):

Cell Proliferation ◽

Mammalian Species ◽

Embryo Implantation ◽

Preimplantation Development ◽

Protein Isoforms ◽

Specific Expression ◽

Promote Cell Proliferation ◽

Alternative Protein ◽

Evolutionarily Conserved ◽

Species Specific

Retrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1ΔN isoform to promote cell proliferation. Cdk2ap1ΔN functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1ΔN, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1ΔN expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.

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Histone chaperone ASF1B promotes human β-cell proliferation via recruitment of histone H3.3

Cell Cycle ◽

10.1080/15384101.2016.1241914 ◽

2016 ◽

Vol 15 (23) ◽

pp. 3191-3202 ◽

Cited By ~ 8

Author(s):

Pradyut K. Paul ◽

Mary E. Rabaglia ◽

Chen-Yu Wang ◽

Donald S. Stapleton ◽

Ning Leng ◽

...

Keyword(s):

Cell Proliferation ◽

Histone Chaperone ◽

Β Cell ◽

Histone H3.3

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Fibroblasts During Hypertrophic Scar Formation and Resolution

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072587 ◽

1973 ◽

Vol 31 ◽

pp. 428-429

Author(s):

C. W. Kischer

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Cell Proliferation ◽

Fine Structure ◽

Metabolic Activity ◽

Hypertrophic Scar ◽

Normal Skin ◽

Ground Substance ◽

Hypertrophic Scars ◽

Scanning Electron

The morphology of the fibroblasts changes markedly as the healing period from burn wounds progresses, through development of the hypertrophic scar, to resolution of the scar by a self-limiting process of maturation or therapeutic resolution. In addition, hypertrophic scars contain an increased cell proliferation largely made up of fibroblasts. This tremendous population of fibroblasts seems congruous with the abundance of collagen and ground substance. The fine structure of these cells should reflect some aspects of the metabolic activity necessary for production of the scar, and might presage the stage of maturation.A comparison of the fine structure of the fibroblasts from normal skin, different scar types, and granulation tissue has been made by transmission (TEM) and scanning electron microscopy (SEM).

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The Effect of Androgen Depletion and Replacement on the Epithelium of the Seminal Vesicle of the Aging Rat

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100116577 ◽

1975 ◽

Vol 33 ◽

pp. 590-591

Author(s):

Venita F. Allison

Keyword(s):

Cell Proliferation ◽

Seminal Vesicle ◽

Male Rats ◽

Target Cells ◽

Cell Regeneration ◽

Secretory Function ◽

Electron Microscopic ◽

Aging Rat ◽

Microscopic Studies ◽

Androgen Depletion

In 1930, Moore, Hughes and Gallager reported that after castration seminal vesicle epithelial cell atrophy occurred and that cell regeneration could be achieved with daily injections of testis extract. Electron microscopic studies have confirmed those observations and have shown that testosterone injections restore the epithelium of the seminal vesicle in adult castrated male rats. Studies concerned with the metabolism of androgens point out that dihydrotestosterone stimulates cell proliferation and that other metabolites of testosterone probably influence secretory function in certain target cells.Although the influence of androgens on adult seminal vesicle epithelial cytology is well documented, little is known of the effect of androgen depletion and replacement on those cells in aging animals. The present study is concerned with the effect of castration and testosterone injection on the epithelium of the seminal vesicle of aging rats.

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Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012895x ◽

1987 ◽

Vol 45 ◽

pp. 934-935

Author(s):

S.S. Poolsawat ◽

C.A. Huerta ◽

S.TY. Lae ◽

G.A. Miranda

Keyword(s):

Cell Proliferation ◽

Liver Function ◽

Chronic Inflammation ◽

Foam Cell ◽

Term Effect ◽

Short Term ◽

Drug Induced ◽

Experimental Induction ◽

Tissue Alterations ◽

Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

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