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4. Human microglial state dynamics in Alzheimer’s disease progression

Author

Sun, Na, Victor, Matheus B., Park, Yongjin P., Xiong, Xushen, Scannail, Aine Ni, Leary, Noelle, Prosper, Shaniah, Viswanathan, Soujanya, Luna, Xochitl, Boix, Carles A., James, Benjamin T., Tanigawa, Yosuke, Galani, Kyriaki, Mathys, Hansruedi, Jiang, Xueqiao, Ng, Ayesha P., Bennett, David A., Tsai, Li-Huei, and Kellis, Manolis

Published
2023
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5. Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells

Author

Harry Kane, Nelson M LaMarche, Áine Ní Scannail, Amanda E Garza, Hui-Fern Koay, Adiba I Azad, Britta Kunkemoeller, Brenneth Stevens, Michael B Brenner, and Lydia Lynch

Subjects
iNKT cells, activation, transcriptional remodeling, adipose tissue, scRNA-Seq, cellular metabolism, Medicine, Science, Biology (General), QH301-705.5
Abstract

Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation in response to non-peptide antigens, such as lipids. While the transcriptional profiles of naive, effector, and memory adaptive T cells have been well studied, less is known about the transcriptional regulation of different iNKT cell activation states. Here, using single-cell RNA-sequencing, we performed longitudinal profiling of activated murine iNKT cells, generating a transcriptomic atlas of iNKT cell activation states. We found that transcriptional signatures of activation are highly conserved among heterogeneous iNKT cell populations, including NKT1, NKT2, and NKT17 subsets, and human iNKT cells. Strikingly, we found that regulatory iNKT cells, such as adipose iNKT cells, undergo blunted activation and display constitutive enrichment of memory-like cMAF+ and KLRG1+ populations. Moreover, we identify a conserved cMAF-associated transcriptional network among NKT10 cells, providing novel insights into the biology of regulatory and antigen-experienced iNKT cells.

Published
2022
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9. Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity

Author

Victor, Matheus B., primary, Leary, Noelle, additional, Luna, Xochitl, additional, Meharena, Hiruy S., additional, Scannail, Aine Ni, additional, Bozzelli, P. Lorenzo, additional, Samaan, George, additional, Murdock, Mitchell H., additional, von Maydell, Djuna, additional, Effenberger, Audrey H., additional, Cerit, Oyku, additional, Wen, Hsin-Lan, additional, Liu, Liwang, additional, Welch, Gwyneth, additional, Bonner, Maeve, additional, and Tsai, Li-Huei, additional

Published
2022
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10. Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity

Author

Matheus B. Victor, Noelle Leary, Xochitl Luna, Hiruy S. Meharena, Aine Ni Scannail, P. Lorenzo Bozzelli, George Samaan, Mitchell H. Murdock, Djuna von Maydell, Audrey H. Effenberger, Oyku Cerit, Hsin-Lan Wen, Liwang Liu, Gwyneth Welch, Maeve Bonner, and Li-Huei Tsai

Subjects
Neurons, Alzheimer Disease, Apolipoprotein E4, Genetics, Apolipoprotein E3, Molecular Medicine, Humans, Cell Biology, Microglia
Abstract

Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing sporadic Alzheimer's disease. How the interaction of APOE4 microglia with neurons differs from microglia expressing the disease-neutral APOE3 allele remains unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect the impact of APOE4 in neuron-microglia communication. Our results reveal that APOE4 induces a lipid-accumulated state that renders microglia weakly responsive to neuronal activity. By examining the transcriptional signatures of APOE3 versus APOE4 microglia in response to neuronal conditioned media, we established that neuronal cues differentially induce a lipogenic program in APOE4 microglia that exacerbates pro-inflammatory signals. Through decreased uptake of extracellular fatty acids and lipoproteins, we identified that APOE4 microglia disrupts the coordinated activity of neuronal ensembles. These findings suggest that abnormal neuronal network-level disturbances observed in Alzheimer's disease patients harboring APOE4 may in part be triggered by impairment in lipid homeostasis in non-neuronal cells.

Published
2022

11. Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells

Author

Kane, H, LaMarche, NM, Ni Scannail, A, Garza, AE, Koay, H-F, Azad, A, Kunkenmoeller, B, Stevens, B, Brenner, MB, Lynch, L, Kane, H, LaMarche, NM, Ni Scannail, A, Garza, AE, Koay, H-F, Azad, A, Kunkenmoeller, B, Stevens, B, Brenner, MB, and Lynch, L

Abstract

Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation in response to non-peptide antigens, such as lipids. While the transcriptional profiles of naive, effector, and memory adaptive T cells have been well studied, less is known about the transcriptional regulation of different iNKT cell activation states. Here, using single-cell RNA-sequencing, we performed longitudinal profiling of activated murine iNKT cells, generating a transcriptomic atlas of iNKT cell activation states. We found that transcriptional signatures of activation are highly conserved among heterogeneous iNKT cell populations, including NKT1, NKT2, and NKT17 subsets, and human iNKT cells. Strikingly, we found that regulatory iNKT cells, such as adipose iNKT cells, undergo blunted activation and display constitutive enrichment of memory-like cMAF+ and KLRG1+ populations. Moreover, we identify a conserved cMAF-associated transcriptional network among NKT10 cells, providing novel insights into the biology of regulatory and antigen-experienced iNKT cells.

Published
2022

12. Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells

Author

Harry Kane, Nelson M. LaMarche, Áine Ní Scannail, Michael B. Brenner, and Lydia Lynch

Abstract

Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation in response to non-peptide antigens, such as lipids. While the transcriptional profiles of naive, effector and memory adaptive T cells have been well studied, less is known about transcriptional regulation of different iNKT cell activation states. Here, using single cell RNA-sequencing, we performed longitudinal profiling of activated iNKT cells, generating a transcriptomic atlas of iNKT cell activation states. We found that transcriptional signatures of activation are highly conserved among heterogeneous iNKT cell populations, including NKT1, NKT2 and NKT17 subsets, and human iNKT cells. Strikingly, we found that regulatory iNKT cells, such as adipose iNKT cells, undergo blunted activation, and display constitutive enrichment of memory-like cMAF+ and KLRG1+ populations. Moreover, we identify a conserved cMAF-associated transcriptional network among NKT10 cells, providing novel insights into the biology of regulatory and antigen experienced iNKT cells.

Published
2021

15. Baile Mhúirne (C.)

Author

Baile Mhúirne (C.), Bhuachalla, Eibhlín, Chárthaigh, Siobhán Ní, Loingsig, Cáit Ní, Chéilleachair, Máire B. Ní, Scannail, Siobhán Ní, Chárthaigh, S. Ní, Ceilleachair, Máire B. Ní, and Céilleachair, Máire B. Ní

Subjects
Baile Bhuirne, Folk poetry, Ballyvourney, Supernatural beings, Folklore, Prayers
Abstract

A collection of folklore and local history stories from Baile Mhúirne (C.) (school) (Ballyvourney, Co. Cork), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Eibhlín, Bean Uí Bhuachalla., Séamus agus A Bhean / Chárthaigh, Siobhán Ní -- Fionn agus an Fear Beag / Chárthaigh, Siobhán Ní -- Bhean agus na Púcaí -- Fear Díomhaoin / Chárthaigh, Siobhán Ní -- Meascán Mearaí / Loingsig, Cáit Ní -- Láirín Dubh agus an Seanduine / Chárthaigh, Siobhán Ní -- Seán agus an Fear Beag / Chéilleachair, Máire B. Ní -- Seán agus an Muicíu Ruadh / Chárthaigh, Siobhán Ní -- Buachaill Drochmhúinte / Chéilleachair, Máire B. Ní -- Bheirt Mhic / Scannail, Siobhán Ní -- An Buachaill Rathmhar / Chárthaigh, Siobhán Ní -- Paidir / Chéilleachair, Máire B. Ní -- Paidir / Chéilleachair, Máire B. Ní -- Rócáin / Chéilleachair, Máire B. Ní -- Aisling / Chéilleachair, Máire B. Ní -- Paidir do Dhuine ar Leabaidh A Bháis / Chéilleachair, Máire B. Ní -- Rócán / Chárthaigh, Siobhán Ní -- Rócán / Chéilleachair, Máire B. Ní -- Amhrán / Chéilleachair, Máire B. Ní -- Mattie agus A Chomrádaí i gCorcaigh / Chéilleachair, Máire B. Ní -- Fear agus an Púca / Chárthaigh, S. Ní -- Fear Misniúil / Chéilleachair, Máire B. Ní -- Bhean ós na hUllánaibh agus an Corda Piseogach / Chéilleachair, Máire B. Ní -- Bhean gan Chaint / Chárthaigh, Siobhán Ní -- Fear ó Shráid a' Mhuilinn / Chéilleachair, Máire B. Ní -- Sprid i gCathair Chéarnaigh / Chéilleachair, Máire B. Ní -- Fear a Théadh Amach / Chéilleachair, Máire B. Ní -- Tincéir agus na Daoine / Chárthaigh, Siobhán Ní -- Seán agus an Fearín Cliste / Chéilleachair, Máire B. Ní -- Fear Misniúil agus an Caitín Draíochta / Chéilleachair, Máire B. Ní -- Eoghan Rua agus an Sagart / Chéilleachair, Máire B. Ní -- Cailín Ciallmhar / Chárthaigh, Siobhán Ní -- Buachaill agus an Sprid / Chárthaigh, Siobhán Ní -- Fear Draíochta / Chéilleachair, Máire B. Ní -- Tadhg agus an tÉan Draíochta / Chéilleachair, Máire B. Ní -- Tomás Óg agus A Chuid Airgid / Chéilleachair, Máire B. Ní -- Fearín Beag Liath / Chéilleachair, Máire B. Ní -- Lánú Aerach / Chárthaigh, Siobhán Ní -- Fear agus A Mhac -- Cailín Bocht / Chéilleachair, Máire B. Ní -- Micheál Dubh / Chéilleachair, Máire B. Ní -- Dómhnall Ó Murchada / Chéilleachair, Máire B. Ní -- Fear Beag / Chéilleachair, Máire B. Ní -- Sean-Nós / Chéilleachair, Máire B. Ní -- Fear Beag Misniúil / Chéilleachair, Máire B. Ní -- Sagart agus an Diabhal / Chárthaigh, Siobhán Ní -- Poll a Trí Sheáin / Chéilleachair, Máire B. Ní -- Fear agus na Pucaí / Chéilleachair, Máire B. Ní -- Fear agus Seán na Gealaí / Chéilleachair, Máire B. Ní -- Seán agus an tÓr / Chéilleachair, Máire B. Ní -- Fear agus na Púcaí sa Lios / Chéilleachair, Máire B. Ní -- Fear agus an tAsal agus na Púcaí / Chéilleachair, Máire B. Ní -- Chlann Mhór / Chárthaigh, Siobhán Ní -- Na Gabhair / Chéilleachair, Máire B. Ní -- Gadaí Dubh agus an Fear / Chárthaigh, Siobhán Ní -- Pádraig na Cainte Greannmhaire agus Dúdóg an Phúca / Chárthaigh, Siobhán Ní -- Bhean in Aon Chruth an Phúca / Ceilleachair, Máire B. Ní -- tSeanabhean / Chéilleachair, Máire B. Ní -- Seanín agus an Gadhar Strae / Chéilleachair, Máire B. Ní -- Púca sa Phluais acu / Chéilleachair, Máire B. Ní -- Fear agus na Naoi bPúcaí / Chárthaigh, S. Ní -- Síle agus A Clann Mhór Mhic / Chéilleachair, Máire B. Ní -- Bhean agus na Turasanna / Chéilleachair, Máire B. Ní -- Pádraig agus na Gadhair / Chárthaigh, Siobhán Ní -- Sprid sa Choill / Céilleachair, Máire B. Ní -- Bhean Ghlic agus A Fear / Céilleachair, Máire B. Ní, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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16. Kilmagner, Mainistir Fhearmuighe

Author

Kilmagner, Mainistir Fhearmuighe, Scannail, Séamus Ó, and Intyre, Noreen Mc

Subjects
Irish Travellers (Nomadic people), local legends, Legal status, laws, etc, Toys, Traditional medicine, Manners and customs, Roads, Animal culture, Birds, Religion, Riddles, Land use, Dissenters, Religious, Butter, Cemeteries, Marriage, Potatoes, Weather, Proverbs, Folklore, Prayers
Abstract

A collection of folklore and local history stories from Kilmagner, Mainistir Fhearmuighe (school) (Kilmagner, Co. Cork), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Séamus Ó Scannail., Hidden Treasure / Intyre, Noreen Mc -- Riddles -- Weather -- Marriage Customs -- Penal Days -- Place Names -- Bird-Lore -- Weather -- Marriage Customs -- Penal Days -- Place Names -- Bird-Lore -- Local Cures -- Homemade Toys -- Lore of Certain Days -- Travelling Folk -- Fairy Places -- Local Roads -- Local District -- Holy Wells -- Herbs -- Potato Crop -- Proverbs -- Festival Customs -- Churning -- Festival Customs -- Domestic Animals -- A Bad Land-Agent -- Story of Richard Oliver -- Another Bad Land-Agent -- Graveyards -- Prayers -- Religious Stories - The Mass, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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17. Clondulane, Mainistir Fhearmuighe

Author

Clondulane, Mainistir Fhearmuighe, Scannail, Aindrias Ó, Cochláin, Seán Ó, Ailgheanáin, Tadhg Ó H, Mhaghramha, Treasa Ní, Dhonnabháin, Eibhlín Ní, Brien, Joan O', Hallinan, John, and Ailgeanáin, Tadhg Ó H

Subjects
History, Legal status, laws, etc, Manners and customs, Severe storms, Riddles, Signs and symbols, Occupations, Marriage, Potatoes, Weather, Poverty, Folklore, Jokes, legendary creatures, Schools, Commerce, Traditional medicine, Supernatural beings, Dwellings, Roads, Shoes, Religion, Famine, 1845-1852, Ringforts, Clothing and dress, Food, Land use, Dissenters, Religious, Recreation, Ireland, Proverbs
Abstract

A collection of folklore and local history stories from Clondulane, Mainistir Fhearmuighe (school) (Clondulane, Co. Cork), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Aindrias Ó Scannail., Hidden Treasure / Cochláin, Seán Ó -- Funny Story / Ailgheanáin, Tadhg Ó h -- Funny Story / Cochláin, Seán Ó -- Weather-Lore / Ailgheanáin, Tadhg Ó h -- Riddles / Cochláin, Seán Ó -- Local Heroes / Mhaghramha, Treasa Ní -- Local Happenings / Dhonnabháin, Eibhlín Ní -- Severe Weather / Brien, Joan O' -- Old Schools / Ailgheanáin, Tadhg Ó h -- One of Cromwell's officers was given Caneysville as a reward for his services, in his work of pillaging the country. / Hallinan, John -- Old Crafts / Cochláin, Seán Ó -- Local Marriage Customs / Ailgheanáin, Tadhg Ó h -- Penal Times / Cochláin, Seán Ó -- Local Cures / Cochláin, Seán Ó -- Lore of Certain Days / Ailgheanáin, Tadhg Ó h -- Fairy Forts / Cochláin, Seán Ó -- Famine Times / Ailgheanáin, Tadhg Ó h -- Local Roads / Cochláin, Seán Ó -- Our Holy Wells / Ailgheanáin, Tadhg Ó h -- Herbs / Cochláin, Seán Ó -- Potato Crop / Cochláin, Seán Ó -- Proverbs / Ailgheanáin, Tadhg Ó h -- Festival Customs / Cochláin, Seán Ó -- Care of the Feet / Ailgheanáin, Tadhg Ó h -- Clothes Made Locally / Cochláin, Seán Ó -- Local Patron Saint / Cochláin, Seán Ó -- Local Fairs / Ailgheanáin, Tadhg Ó h -- Local Landlords / Ailgheanáin, Tadhg Ó h -- Food in Olden Times / Ailgheanáin, Tadhg Ó h -- Hurling and Football Matches / Cochláin, Seán Ó -- Old Story / Ailgheanáin, Tadhg Ó h -- Old Irish Tales / Cochláin, Seán Ó -- Buying and Selling / Ailgheanáin, Tadhg Ó h -- Old Houses / Cochláin, Seán Ó -- Stories of Giants and Warriors - Fionn Mac Cool and the Giant / Ailgheanáin, Tadhg Ó h -- Local Ruins / Cochláin, Seán Ó -- Religious Stories / Ailgheanáin, Tadhg Ó h -- Emblems and Objects of Value / Cochláin, Seán Ó -- Historical Tradition / Cochláin, Seán Ó -- Strange Animals / Cochláin, Seán Ó -- Meeting of Oisin and Saint Patrick / Ailgeanáin, Tadhg Ó h -- Old Story / Cochláin, Seán Ó, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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18. Ardee (De la Salle)

Author

Ardee (De La Salle) and Scannail, P. Ó

Subjects
Historic sites, Folk poetry, Legal status, laws, etc, Traditional medicine, Folk beliefs, Verbal arts and literature, Manners and customs, May (Month), Smithing, Dissenters, Religious, Signs and symbols, Cemeteries, Ireland, Proverbs, Folklore
Abstract

A collection of folklore and local history stories from Ardee (De la Salle) (school) (Ardee, Co. Louth), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Br. P. Ó Scannail., Linguistic - Irish Words Adopted into English Speech -- Words Not Current in Good English Speech -- Historic -- Topographic -- Foods Discarded During Living Memory -- Folk Cures and Charms -- St Mochta was a local saint... -- None -- See Louth Archaeological Society... -- see 37 -- On May Eve - Buttercups or dandelions thrown on to roof of house... -- Though the local graveyard is not modern... -- Archaeological -- Archaeological -- A person who enters a house in which churning is going on must take a hand at churning... -- Miscellaneous -- Cad Is Ní Bochtán? -- Oileán Dairbhe -- Seo chugat Tomás le ceann árd... -- Seo guidhe a chaula ó shéanfhear in Oileán Árainn... -- Bhí sagart Paróiste i mBaile Mhúirne fadó agus nuair cailltí duine ... -- Seo é an cómhairle a thugadh an sagart ceudna do'n lánamhain a bheadh tar éis a phósadh. -- tSeanbhean agus an Chearc -- Comhairle -- Seanfhocail -- Graveyards in Ardee Parish -- Old Graveyards -- Local Forges, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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19. Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances.

Author

von Maydell D, Wright S, Bonner JM, Staab C, Spitaleri A, Liu L, Pao PC, Yu CJ, Scannail AN, Li M, Boix CA, Mathys H, Leclerc G, Menchaca GS, Welch G, Graziosi A, Leary N, Samaan G, Kellis M, and Tsai LH

Abstract

Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer's disease (odds ratio ∼2), yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 human post-mortem samples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24 matched non-carrier control individuals. ABCA7 LoF was associated with gene expression changes in all major cell types. Excitatory neurons, which expressed the highest levels of ABCA7, showed transcriptional changes related to lipid metabolism, mitochondrial function, cell cycle-related pathways, and synaptic signaling. ABCA7 LoF-associated transcriptional changes in neurons were similarly perturbed in carriers of the common AD missense variant ABCA7 p.Ala1527Gly (n = 240 controls, 135 carriers), indicating that findings from our study may extend to large portions of the at-risk population. Consistent with ABCA7's function as a lipid exporter, lipidomic analysis of isogenic iPSC-derived neurons (iNs) revealed profound intracellular triglyceride accumulation in ABCA7 LoF, which was accompanied by a relative decrease in phosphatidylcholine abundance. Metabolomic and biochemical analyses of iNs further indicated that ABCA7 LoF was associated with disrupted mitochondrial bioenergetics that suggested impaired lipid breakdown by uncoupled respiration. Treatment of ABCA7 LoF iNs with CDP-choline (a rate-limiting precursor of phosphatidylcholine synthesis) reduced triglyceride accumulation and restored mitochondrial function, indicating that ABCA7 LoF-induced phosphatidylcholine dyshomeostasis may directly disrupt mitochondrial metabolism of lipids. Treatment with CDP-choline also rescued intracellular amyloid β -42 levels in ABCA7 LoF iNs, further suggesting a link between ABCA7 LoF metabolic disruptions in neurons and AD pathology. This study provides a detailed transcriptomic atlas of ABCA7 LoF in the human brain and mechanistically links ABCA7 LoF-induced lipid perturbations to neuronal energy dyshomeostasis. In line with a growing body of evidence, our study highlights the central role of lipid metabolism in the etiology of Alzheimer's disease.

Published
2024
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