A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Glucose-6-phosphate dehydrogenase activity measured by spectrophotometry and associated genetic variants from the Oromiya zone, Ethiopia

BACKGROUND: The study aimed to gain first data on the prevalence of G6PD enzyme deficiency measured by spectrophotometry and associated genetic variants in Jimma and surroundings, Ethiopia. The area is a Plasmodium vivax endemic region, but 8-aminoquinolines such as primaquine are not recommended as G6PD testing is not available. METHODS: Healthy volunteers were recruited at Jimma University, Ethiopia. Enzyme activity was tested by spectrophotometry at the University of Ulm, Germany. A G6PD RDT (Binax NOW((R)) G6PD, Alere, USA) was additionally performed. The G6PD gene was analysed for polymorphisms in a sub-population. Tests for haemoglobinopathies and the presence of malaria parasites were conducted. RESULTS: No severe or moderate (cut-off 60%) G6PD deficiency was found in 206 volunteers. Median male activity was 6.1 U/g Hb. Eleven participants (5.4%) showed activities between 70 and 80%. No haemoglobinopathy was detected. None of the subjects showed asymptomatic parasitaemia. One G6PD-A+ variant (A376G) and one new non-synonymous mutation (G445A) were found. CONCLUSIONS: As the prevalence of G6PD deficiency seems low in this area, the use of 8-aminoquinolines should be encouraged. However, reliable G6PD testing methods have to be implemented and safe cut-off levels need to be defined

A multimodal cell census and atlas of the mammalian primary motor cortex

none258Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.openCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; McCarroll, Steven A.; McMillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; McCracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, SusanCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; Mccarroll, Steven A.; Mcmillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; Mccracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, Susa