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 characterise the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We identify that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing, as well as for proper mitochondrial energetics in embryonic stem cells. Moreover, forcing Lima1 expression enables primed mouse and human pluripotent stem cells to be incorporated into murine pre-implantation embryos. Thus, Lima1 is a key effector molecule that mediates the pluripotency control of membrane dynamics and cellular metabolism.
Additional Information
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 05 May 2021; Accepted 10 January 2022; Published 01 February 2022. We thank Prof. Dr Rolf Kemler for the fruitful discussions and continuous support; Prof. Hans R. Schöler, Prof. Dr Ralf H. Adams and Prof. Dr Dietmar Vestweber (MPI-MB) for providing access to key infrastructure, equipment and reagents; Prof. Dr Roland Wedlich-Söldner (University of Münster) for sharing reagents; Prof. Dr Masatoshi Takeichi (RIKEN Center for Developmental Biology) for providing Lima1 antibody and plasmids; Dr Anika Witten for the RNA sequencing, Prof. Hubert Schorle (University of Bonn) for sharing TSC, Kirill Salewskij and all members of the Embryonic Self-Organization research group and the Department of Cell and Developmental Biology (MPI-MB) for the fruitful discussions and suggestions and Dr Celeste Brennecka for proofreading the manuscript. This work was supported by the German Research Foundation (DFG) grant BE-5800/2-1 and DFG Emmy Noether grant BE-5800/1-1 to I.B.; Wellcome Trust (098287/Z/12/Z) and ERC (669198) grants to M.Z.-G.; B.D. is a member of and was supported by the CiM/IMPRS joint Graduate School. Open Access funding enabled and organized by Projekt DEAL. Data availability: The RNA-seq data generated in this study have been deposited in the ArrayExpress database under accession code "E-MTAB-10301". The proteomics data data data generated in this study have been deposited in the ProteomeXchange database under accession code " PXSD025293". Uniprot database UP000005640_9606.fasta; version April 2019 used for Mass Spectrometry analysis is available at "Uniprot [ftp://ftp.uniprot.org/pub/databases/uniprot/previous_releases/release-2019_04/knowledgebase/]". All other relevant data supporting the key findings of this study are available within the article and its Supplementary Information files or from the corresponding author upon reasonable request. Source data are provided with this paper. Author Contributions: I.B. and B.D. conceived the study and designed the experiments; B.D. performed most of the experiments; F.G. and J.M.V. performed the bioinformatical analysis; B.R., M.-T.B. and K.B.B. performed the Seahorse measurements; H.C.A.D. performed the mass spectrometry; H.B. performed histology; L.K. did the embryo transfers; K.M. and D.Z. performed ultrastructural analysis; M.S. assisted with FACS and FlowJo analysis; M.Z.-G. and M.P.S. provided access to key infrastructure and critical discussion of the manuscript; I.B. and B.D. wrote the manuscript. The authors declare no competing interests. Peer review information: Nature Communications thanks Jiyeon Kim and the other anonymous reviewer(s) for their contribution to the peer review of this work.Attached Files
Published - s41467-022-28139-5.pdf
Supplemental Material - 41467_2022_28139_MOESM10_ESM.xlsx
Supplemental Material - 41467_2022_28139_MOESM1_ESM.pdf
Supplemental Material - 41467_2022_28139_MOESM2_ESM.docx
Supplemental Material - 41467_2022_28139_MOESM3_ESM.xlsx
Supplemental Material - 41467_2022_28139_MOESM4_ESM.xlsx
Supplemental Material - 41467_2022_28139_MOESM5_ESM.xlsx
Supplemental Material - 41467_2022_28139_MOESM6_ESM.xlsx
Supplemental Material - 41467_2022_28139_MOESM7_ESM.avi
Supplemental Material - 41467_2022_28139_MOESM8_ESM.avi
Supplemental Material - 41467_2022_28139_MOESM9_ESM.pdf
Files
| Name | Size | Download all |
|---|---|---|
|
md5:162bf5a208bcb74bf26e5e609a3c23a5
|
69.9 kB | Download |
|
md5:540be3747e70a7979ad150479f134f3a
|
12.5 kB | Download |
|
md5:7a827f5afb3ece263cf82bae43291af4
|
682.9 kB | Download |
|
md5:8cda12db54ebfab5257057c8b903d7b5
|
5.0 MB | Preview Download |
|
md5:2b389f6db2f92b380964a68931ba6c47
|
331.4 kB | Preview Download |
|
md5:2d152736e4c6367630602769f8dee0a3
|
2.2 MB | Download |
|
md5:2ba72b9c07a7eda5ca565cb51051c7ae
|
513.1 kB | Download |
|
md5:1c575469c7509338070308eda0aae3c1
|
19.1 kB | Download |
|
md5:777ff2ff160d3d282635aaeaff8edb7c
|
13.0 MB | Preview Download |
|
md5:d84d58f7179f7bba7eb84edabc1d9a0c
|
2.3 MB | Download |
|
md5:2eed9a7e37a9191592606dd31b03f5ab
|
2.4 MB | Download |
Additional details
- PMCID
- PMC8807836
- Eprint ID
- 113200
- Resolver ID
- CaltechAUTHORS:20220201-160162400
- Deutsche Forschungsgemeinschaft (DFG)
- BE-5800/2-1
- Deutsche Forschungsgemeinschaft (DFG)
- BE-5800/1-1
- Wellcome Trust
- 098287/Z/12/Z
- European Research Council (ERC)
- 669198
- CiM/IMPRS Joint Graduate School
- Projekt DEAL
- Created
-
2022-02-01Created from EPrint's datestamp field
- Updated
-
2022-02-08Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering (BBE)