[ { "id": "authors:0j638-jx111", "collection": "authors", "collection_id": "0j638-jx111", "cite_using_url": "https://authors.library.caltech.edu/records/0j638-jx111", "type": "article", "title": "Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease", "author": [ { "family_name": "Polonsky", "given_name": "Michal", "orcid": "0000-0003-3871-460X", "clpid": "Polonsky-Michal" }, { "family_name": "Gerhardt", "given_name": "Louisa M. S." }, { "family_name": "Yun", "given_name": "Jina", "clpid": "Yun-Chi-H-Jina" }, { "family_name": "Koppitch", "given_name": "Kari" }, { "family_name": "Col\u00f3n", "given_name": "Katsuya Lex", "orcid": "0000-0002-7347-6128", "clpid": "Col\u00f3n-Katsuya-Lex" }, { "family_name": "Amrhein", "given_name": "Henry", "orcid": "0000-0002-4264-140X", "clpid": "Amrhein-H" }, { "family_name": "Wold", "given_name": "Barbara", "orcid": "0000-0003-3235-8130", "clpid": "Wold-B-J" }, { "family_name": "Zheng", "given_name": "Shiwei" }, { "family_name": "Yuan", "given_name": "Guo-Cheng", "orcid": "0000-0002-2283-4714" }, { "family_name": "Thomson", "given_name": "Matt", "orcid": "0000-0003-1021-1234", "clpid": "Thomson-M-W" }, { "family_name": "Cai", "given_name": "Long", "orcid": "0000-0002-7154-5361", "clpid": "Cai-Long" }, { "family_name": "McMahon", "given_name": "Andrew P.", "orcid": "0000-0002-3779-1729", "clpid": "McMahon-Andrew-P" } ], "abstract": "

Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, together with injury-invoked inflammation and fibrosis. Deciphering the molecular pathways and cellular interactions driving these processes is challenging due to the complex tissue structure. Here, we apply single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics reveals injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicts Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and their neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis identifies cellular microenvironments resembling early tertiary lymphoid structures and associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

", "doi": "10.1038/s41467-024-51186-z", "pmcid": "PMC11377535", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2024-09-05", "series_number": "1", "volume": "15", "issue": "1", "pages": "7010" }, { "id": "authors:pqcc0-ndz62", "collection": "authors", "collection_id": "pqcc0-ndz62", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211013-205829700", "type": "article", "title": "Dynamic changes in tRNA modifications and abundance during T cell activation", "author": [ { "family_name": "Rak", "given_name": "Roni", "clpid": "Rak-Roni" }, { "family_name": "Polonsky", "given_name": "Michal", "orcid": "0000-0003-3871-460X", "clpid": "Polonsky-Michal" }, { "family_name": "Eizenberg-Magar", "given_name": "Inbal", "orcid": "0000-0001-6940-6226", "clpid": "Eizenberg-Magar-Inbal" }, { "family_name": "Mo", "given_name": "Yufeng", "clpid": "Mo-Yufeng" }, { "family_name": "Sakaguchi", "given_name": "Yuriko", "clpid": "Sakaguchi-Yuriko" }, { "family_name": "Mizrahi", "given_name": "Orel", "clpid": "Mizrahi-Orel" }, { "family_name": "Nachshon", "given_name": "Aharon", "orcid": "0000-0003-2283-5220", "clpid": "Nachshon-Aharon" }, { "family_name": "Reich-Zeliger", "given_name": "Shlomit", "clpid": "Reich-Zeliger-Shlomit" }, { "family_name": "Stern-Ginossar", "given_name": "Noam", "orcid": "0000-0003-3583-5932", "clpid": "Stern-Ginossar-Noam" }, { "family_name": "Dahan", "given_name": "Orna", "orcid": "0000-0002-8096-5085", "clpid": "Dahan-Orna" }, { "family_name": "Suzuki", "given_name": "Tsutomu", "clpid": "Suzuki-Tsutomu" }, { "family_name": "Friedman", "given_name": "Nir", "orcid": "0000-0002-1078-3921", "clpid": "Friedman-Nir" }, { "family_name": "Pilpel", "given_name": "Yitzhak", "clpid": "Pilpel-Yitzhak" } ], "abstract": "The tRNA pool determines the efficiency, throughput, and accuracy of translation. Previous studies have identified dynamic changes in the tRNA (transfer RNA) supply and mRNA (messenger RNA) demand during cancerous proliferation. Yet dynamic changes may also occur during physiologically normal proliferation, and these are less well characterized. We examined the tRNA and mRNA pools of T cells during their vigorous proliferation and differentiation upon triggering their antigen receptor. We observed a global signature of switch in demand for codons at the early proliferation phase of the response, accompanied by corresponding changes in tRNA expression levels. In the later phase, upon differentiation, the response of the tRNA pool relaxed back to the basal level, potentially restraining excessive proliferation. Sequencing of tRNAs allowed us to evaluate their diverse base-modifications. We found that two types of tRNA modifications, wybutosine and ms2t6A, are reduced dramatically during T cell activation. These modifications occur in the anticodon loops of two tRNAs that decode \"slippery codons,\" which are prone to ribosomal frameshifting. Attenuation of these frameshift-protective modifications is expected to increase the potential for proteome-wide frameshifting during T cell proliferation. Indeed, human cell lines deleted of a wybutosine writer showed increased ribosomal frameshifting, as detected with an HIV gag-pol frameshifting site reporter. These results may explain HIV's specific tropism toward proliferating T cells since it requires ribosomal frameshift exactly on the corresponding codon for infection. The changes in tRNA expression and modifications uncover a layer of translation regulation during T cell proliferation and expose a potential tradeoff between cellular growth and translation fidelity.", "doi": "10.1073/pnas.2106556118", "pmcid": "PMC8594584", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences", "publication_date": "2021-10-19", "series_number": "42", "volume": "118", "issue": "42", "pages": "Art. No. e2106556118" } ]