Histopathology

histo.png

The Histopathology Core provides technical histology and interpretive pathology services to support IMS-MRL researchers and the greater scientific community. 

Routine histology techniques include processing, embedding, and sectioning of fixed and frozen samples. Staining options range from Haematoxylin and Eosin (H&E) to special stains such as Picrosirius Red and Masson's Trichrome.

The Core uses a Leica Bond RX autostainer to run high-throughput single and multiplex immunohistochemistry (IHC) and immunofluorescence (IF) assays. Automated in situ hybridisation (ISH) is available through RNAscope by ACD Bio. RNAscope uses a proprietary probe design to amplify target-specific signals but not background noise from non-specific hybridisation. The assay can label up to four RNA targets in a single section and can combine with IHC to demonstrate protein/RNA co-localisation in a single section.

Histopathology offers one-to-one sessions with a pathologist for slide reviews and training. Our pathologists can also provide quantitative analysis reports and images for publication. The Core can access additional support from pathologists with various specialities where required. 

Services provided

Technical Histology:

• Study design and optimisation relevant to histology endpoints
• Advice and assistance on collecting, trimming, sectioning, and staining fixed and frozen tissue
• Processing of formalin-fixed samples to paraffin wax block (whole tissue and cell lines)
• Fixed and frozen sectioning
• H&E staining
• Special stains
• IHC and IF optimisation and staining (commercial and novel antibodies, single and multiplex)
• ISH (RNAscope)
• IHC/ISH co-staining
• Training and supervision (IMS & University of Cambridge only)

Interpretive Pathology:

• Development of protocols for pathology endpoints
• One-to-one slide review
• Pathology/morphology teaching
• Quantitative analysis of pathological findings
• Preparation of reports and images for publication

Instruments available

• Leica RM2255 rotary microtome 
• Leica CM1950 cryostat 
• Thermo HistoStar embedding centre 
• Leica BOND RX autostainer
• Sakura VIP6 tissue processor

Recent publications

IMS

• Tan J, Virtue S, Norris DM, Conway OJ, Yang M, Bidault G, Gribben C, Lugtu F, Kamzolas I, Krycer JR, Mills RJ, Liang L, Pereira C, Dale M, Shun-Shion AS, Baird HJ, Horscroft JA, Sowton AP, Ma M, Carobbio S, Petsalaki E, Murray AJ, Gershlick DC, Nathan JA, Hudson JE, Vallier L, Fisher-Wellman KH, Frezza C, Vidal-Puig A, Fazakerley DJ. Limited oxygen in standard cell culture alters metabolism and function of differentiated cells. EMBO J. 2024 Apr 5. doi: 10.1038/s44318-024-00084-7.

• Kincaid JWR, Rimmington D, Tadross JA, Cimino I, Zvetkova I, Kaser A, Richards P, Patel S, O'Rahilly S, Coll AP. The gastrointestinal tract is a major source of the acute metformin-stimulated rise in GDF15. Sci Rep. 2024 Jan 22;14(1):1899. doi: 10.1038/s41598-024-51866-2.

• Adriaenssens A, Broichhagen J, de Bray A, Ast J, Hasib A, Jones B, Tomas A, Burgos NF, Woodward O, Lewis J, O'Flaherty E, El K, Cui C, Harada N, Inagaki N, Campbell J, Brierley D, Hodson DJ, Samms R, Gribble F, Reimann F. Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding. JCI Insight. 2023 May 22;8(10):e164921. doi: 10.1172/jci.insight.164921.

• Mann JP, Duan X, Patel S, Tábara LC, Scurria F, Alvarez-Guaita A, Haider A, Luijten I, Page M, Protasoni M, Lim K, Virtue S, O’Rahilly S, Armstrong M, Prudent J, Semple RK, Savage DB. A mouse model of human mitofusin 2-related lipodystrophy exhibits adipose-specific mitochondrial stress and reduced leptin secretion. Elife. 2023 Feb 1;12:e82283. doi: 10.7554/eLife.82283.

• Patel S, Haider A, Alvarez-Guaita A, Bidault G, El-Sayed Moustafa JS, Guiu-Jurado E, Tadross JA, Warner J, Harrison J, Virtue S, Scurria F, Zvetkova I, Blüher M, Small KS, O’Rahilly S, Savage DB. Combined genetic deletion of GDF15 and FGF21 has modest effects on body weight, hepatic steatosis and insulin resistance in high fat fed mice. Mol Metab. 2022 Nov;65:101589. doi: 10.1016/j.molmet.2022.101589.

• Schoonejans JM, Blackmore HL, Ashmore TJ, Pantaleão LC, Pellegrini Pisani L, Dearden L, Tadross JA, Aiken CE, Fernandez-Twinn DS, Ozanne SE. Sex-specific effects of maternal metformin intervention during glucose-intolerant obese pregnancy on body composition and metabolic health in aged mouse offspring. Diabetologia. 2022 Sep 16. doi: 10.1007/s00125-022-05789-0.

• Pellegrinelli V, Rodriguez-Cuenca S, Rouault C, Figueroa-Juarez E, Schilbert H, Virtue S, Moreno-Navarrete JM, Bidault G, Vázquez-Borrego MC, Dias AR, Pucker B, Dale M, Campbell M, Carobbio S, Lin YH, Vacca M, Aron-Wisnewsky J, Mora S, Masiero MM, Emmanouilidou A, Mukhopadhyay S, Dougan G, den Hoed M, Loos RJF, Fernández-Real JM, Chiarugi D, Clément K, Vidal-Puig A. Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.  Nat Metab. 2022 Apr;4(4):476-494. doi: 10.1038/s42255-022-00561-5.

External

• Young KA, Wojdyla K, Lai T, Mulholland KE, Aldaz Casanova S, Antrobus R, Andrews SR, Biggins L, Mahler-Araujo B, Barton PR, Anderson KR, Fearnley GW, Sharpe HJ. The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression. J Cell Sci. 2024 Jul 15;137(14):jcs261914. doi: 10.1242/jcs.261914.

• Gaccioli F, Stephens K, Sovio U, Jessop F, Wong HS, Lager S, Cook E, de Goffau MC, Le Doare K, Peacock SJ, Parkhill J, Charnock-Jones DS, Smith GCS. Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants. Nat Microbiol. 2023 Dec;8(12):2338-2348. doi: 10.1038/s41564-023-01528-2.

• Rochford AE, Carnicer-Lombarte A, Kawan M, Jin A, Hilton S, Curto VF, Rutz AL, Moreau T, Kotter MRN, Malliaras GG, Barone DG. Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics. Sci Adv. 2023 Mar 22;9(12):eadd8162. doi: 10.1126/sciadv.add8162.

• Rahrmann EP, Shorthouse D, Jassim A, Hu LP, Ortiz M, Mahler-Araujo B, Vogel P, Paez-Ribes M, Fatemi A, Hannon GJ, Iyer R, Blundon JA, Lourenço FC, Kay J, Nazarian RM, Hall BA, Zakharenko SS, Winton DJ, Zhu L, Gilbertson RJ. The NALCN channel regulates metastasis and nonmalignant cell dissemination. Nat Genet. 2022 Dec;54(12):1827-1838. doi: 10.1038/s41588-022-01182-0. 

• Pagano E, Elias JE, Schneditz G, Saveljeva S, Holland LM, Borrelli F, Karlsen TH, Kaser A, Kaneider NC. Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment. Gut. 2022 Mar;71(3):509-520. doi: 10.1136/gutjnl-2020-323363.