A subcellular cookie cutter for spatial genomics in human tissue

Abstract

Intracellular heterogeneity contributes significantly to cellular physiology and, in a number of debilitating diseases, cellular pathophysiology. This is greatly influenced by distinct organelle populations and to understand the aetiology of disease, it is important to have tools able to isolate and differentially analyse organelles from precise location within tissues. Here, we report the development of a subcellular biopsy technology that facilitates the isolation of organelles, such as mitochondria, from human tissue. We compared the subcellular biopsy technology to laser capture microdissection (LCM) that is the state-of-the-art technique for the isolation of cells from their surrounding tissues. We demonstrate an operational limit of >20 µm for LCM and then, for the first time in human tissue, show that subcellular biopsy can be used to isolate mitochondria beyond this limit.

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Item Type:	Article
Authors/Creators:	Bury, AG Pyle, A Marcuccio, F https://orcid.org/0000-0003-4816-2896 Turnbull, DM Vincent, AE Hudson, G Actis, P https://orcid.org/0000-0002-7146-1854
Copyright, Publisher and 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Subcellular; Genomics; SICM; Isolation; Mitochondria; Organelle
Dates:	Published: July 2022 Published (online): 1 March 2022 Accepted: 31 January 2022
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Electronic & Electrical Engineering (Leeds) > Pollard Institute (Leeds)
Funding Information:	Funder Grant number EU - European Union 812398 Royal Society RG160273 EPSRC (Engineering and Physical Sciences Research Council) EP/S01764X/1
Depositing User:	Symplectic Publications
Date Deposited:	16 Feb 2022 16:32
Last Modified:	05 Apr 2023 17:10
Status:	Published
Publisher:	Springer
Identification Number:	10.1007/s00216-022-03944-5
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:183630

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A subcellular cookie cutter for spatial genomics in human tissue

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