Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing

Single-cell RNA sequencing has revolutionized molecular cell biology by enabling the identification of unique transcription profiles and cell transcription states within the same tissue. However, tissue dissociation presents a challenge for non-model organisms, as commercial kits are often incompati...

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Main Authors: Ana Barletta, Octavio Talyuli, Pedro Cecilio, Carolina Barillas-Mury
Format: Article
Language:English
Published: Bio-protocol LLC 2025-06-01
Series:Bio-Protocol
Online Access:https://bio-protocol.org/en/bpdetail?id=5352&type=0
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author Ana Barletta
Octavio Talyuli
Pedro Cecilio
Carolina Barillas-Mury
author_facet Ana Barletta
Octavio Talyuli
Pedro Cecilio
Carolina Barillas-Mury
author_sort Ana Barletta
collection DOAJ
description Single-cell RNA sequencing has revolutionized molecular cell biology by enabling the identification of unique transcription profiles and cell transcription states within the same tissue. However, tissue dissociation presents a challenge for non-model organisms, as commercial kits are often incompatible, and current protocols rely on tissue enzymatic digestion for extended periods. Tissue digestion can alter cell transcription in response to temperature and the stress caused by enzymatic treatment. Here, we propose a protocol to stabilize RNA using a deep eutectic solvent (Vivophix, Rapid Labs) prior to tissue dissociation, thereby avoiding transcription changes induced by the process and preventing RNase activity during incubation. We validated this methodology for three medically important insect vectors: Anopheles gambiae, Aedes aegypti, and Lutzomyia longipalpis. Single-cell RNA sequencing using our insect midgut dissociation protocol yielded high-quality sequencing results, with a high number of cells recovered, a low percentage of mitochondrial reads, and a low percentage of ambient RNA—two hallmark standards of cell quality.
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spelling doaj-art-8018bda95b2d42d2943d9427196bc1482025-08-20T02:20:52ZengBio-protocol LLCBio-Protocol2331-83252025-06-01151210.21769/BioProtoc.5352Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA SequencingAna Barletta0Octavio Talyuli1Pedro Cecilio2Carolina Barillas-Mury3Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health; Rockville, MD, USALaboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health; Rockville, MD, USALaboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health; Rockville, MD, USALaboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health; Rockville, MD, USASingle-cell RNA sequencing has revolutionized molecular cell biology by enabling the identification of unique transcription profiles and cell transcription states within the same tissue. However, tissue dissociation presents a challenge for non-model organisms, as commercial kits are often incompatible, and current protocols rely on tissue enzymatic digestion for extended periods. Tissue digestion can alter cell transcription in response to temperature and the stress caused by enzymatic treatment. Here, we propose a protocol to stabilize RNA using a deep eutectic solvent (Vivophix, Rapid Labs) prior to tissue dissociation, thereby avoiding transcription changes induced by the process and preventing RNase activity during incubation. We validated this methodology for three medically important insect vectors: Anopheles gambiae, Aedes aegypti, and Lutzomyia longipalpis. Single-cell RNA sequencing using our insect midgut dissociation protocol yielded high-quality sequencing results, with a high number of cells recovered, a low percentage of mitochondrial reads, and a low percentage of ambient RNA—two hallmark standards of cell quality.https://bio-protocol.org/en/bpdetail?id=5352&type=0
spellingShingle Ana Barletta
Octavio Talyuli
Pedro Cecilio
Carolina Barillas-Mury
Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
Bio-Protocol
title Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
title_full Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
title_fullStr Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
title_full_unstemmed Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
title_short Optimized Midgut Tissue Dissociation of Mosquitoes and Sandflies for High-Quality Single-Cell RNA Sequencing
title_sort optimized midgut tissue dissociation of mosquitoes and sandflies for high quality single cell rna sequencing
url https://bio-protocol.org/en/bpdetail?id=5352&type=0
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