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Lima1 mediates the pluripotency control of membrane dynamics and cellular metabolism

ABSTRACT: Lima1 is an extensively studied prognostic marker of malignancy and is also considered to be a tumour suppressor, but its role in a developmental context of non-transformed cells is poorly understood. Here, we characterised the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We found that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing. Moreover, Lima1 is essential for proper mitochondrial energetics, which is crucial for the growth of solid tumours. Forcing Lima1 expression enabled human pluripotent stem cells to be incorporated into murine pre-implantation embryos, trespassing the interspecies engraftment barrier. Thus, Lima1 is a key effector molecule that mediates the pluripotency control of membrane dynamics and cellular metabolism.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell

SUBMITTER: Hannes Drexler

LAB HEAD: Hannes C. A. Drexler

PROVIDER: PXD025293 | Pride | 2021-12-16

REPOSITORIES: Pride

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			Action	DRS
	20201127_exp1076_Ben___1_Slot2-19_1_1519.d.7z	Other
	20201127_exp1076_Ben___2_Slot2-20_1_1520.d.7z	Other
	20201127_exp1076_Ben___3_Slot2-21_1_1521.d.7z	Other
	20201127_exp1076_Ben_wo_1_Slot2-16_1_1516.d.7z	Other
	20201127_exp1076_Ben_wo_2_Slot2-17_1_1517.d.7z	Other

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Project description:Despite many improvements with in vitro culture systems, the quality and developmental ability of mammalian embryos produced in vitro is still lower than their in vivo counterparts. To bring knowledge to answer this question, we used a mass spectrometry (MS) approach to compare the protein content of bovine embryos that were conceived in vivo or produced in vitro. A total of 38 pools of grade-1 quality bovine embryos at the 4-6 cell, 8-12 cell, morula, compact morula and blastocyst stages developed either in vivo or in vitro were analyzed by nano-liquid chromatography coupled with label-free quantitative mass spectrometry, allowing the identification of 3,028 proteins. Multivariate analysis of quantified proteins showed a clear separation of embryo pools according to their in vivo or in vitro origin at all stages. Three clusters of differentially abundant proteins (DAPs) according to embryo origin were evidenced, including 463 proteins more abundant in vivo than in vitro across development, and 314 and 222 proteins more abundant in vitro than in vivo before and after the morula stage, respectively. The functional analysis of proteins found more abundant in vivo showed an enrichment in carbohydrate metabolism and cytoplasmic cellular components. Proteins found more abundant in vitro before the morula stage were mostly localized in mitochondrial matrix and involved in ATP-dependent activity while those overabundant after morula stage were mostly localized in the ribonucleoprotein complex and involved in protein synthesis. Oviductin and other proteins previously shown to interact with early embryos in vitro were among the most overabundant proteins after in vivo development. In conclusion, the maternal environment led to faster degradation of mitochondrial proteins at early embryo developmental stages, lower abundance of proteins involved in protein synthesis at the time of embryonic genome activation and a global upregulation of carbohydrate and small molecule metabolic pathways compared to in vitro produced embryos. Furthermore, our data confirm that embryos developed in vivo uptake large amounts of oviduct fluid-derived proteins as soon as the 4-6 cell stage. These data provide new insight into the molecular contribution of the mother to the developmental ability of early embryos and will help designing better in vitro culture systems.

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Lima1 mediates the pluripotency control of membrane dynamics and cellular metabolism

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