@article{amin_generating_2023,
	title = {Generating human neural diversity with a multiplexed morphogen screen in organoids},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312596/},
	doi = {10.1101/2023.05.31.541819},
	abstract = {Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fates
in vitro
often relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards an
in vitro
morphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.},
	urldate = {2024-07-22},
	journal = {bioRxiv},
	author = {Amin, Neal D. and Kelley, Kevin W. and Hao, Jin and Miura, Yuki and Narazaki, Genta and Li, Tommy and McQueen, Patrick and Kulkarni, Shravanti and Pavlov, Sergey and Paşca, Sergiu P.},
	month = jun,
	year = {2023},
	pmid = {37398073},
	pmcid = {PMC10312596},
	keywords = {Collection: Brain Organoids},
	pages = {2023.05.31.541819},
}

{"_id":"5PNcPiZLoTzX5gtki","bibbaseid":"amin-kelley-hao-miura-narazaki-li-mcqueen-kulkarni-etal-generatinghumanneuraldiversitywithamultiplexedmorphogenscreeninorganoids-2023","author_short":["Amin, N. D.","Kelley, K. W.","Hao, J.","Miura, Y.","Narazaki, G.","Li, T.","McQueen, P.","Kulkarni, S.","Pavlov, S.","Paşca, S. P."],"bibdata":{"bibtype":"article","type":"article","title":"Generating human neural diversity with a multiplexed morphogen screen in organoids","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312596/","doi":"10.1101/2023.05.31.541819","abstract":"Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fates in vitro often relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards an in vitro morphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.","urldate":"2024-07-22","journal":"bioRxiv","author":[{"propositions":[],"lastnames":["Amin"],"firstnames":["Neal","D."],"suffixes":[]},{"propositions":[],"lastnames":["Kelley"],"firstnames":["Kevin","W."],"suffixes":[]},{"propositions":[],"lastnames":["Hao"],"firstnames":["Jin"],"suffixes":[]},{"propositions":[],"lastnames":["Miura"],"firstnames":["Yuki"],"suffixes":[]},{"propositions":[],"lastnames":["Narazaki"],"firstnames":["Genta"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Tommy"],"suffixes":[]},{"propositions":[],"lastnames":["McQueen"],"firstnames":["Patrick"],"suffixes":[]},{"propositions":[],"lastnames":["Kulkarni"],"firstnames":["Shravanti"],"suffixes":[]},{"propositions":[],"lastnames":["Pavlov"],"firstnames":["Sergey"],"suffixes":[]},{"propositions":[],"lastnames":["Paşca"],"firstnames":["Sergiu","P."],"suffixes":[]}],"month":"June","year":"2023","pmid":"37398073","pmcid":"PMC10312596","keywords":"Collection: Brain Organoids","pages":"2023.05.31.541819","bibtex":"@article{amin_generating_2023,\n\ttitle = {Generating human neural diversity with a multiplexed morphogen screen in organoids},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312596/},\n\tdoi = {10.1101/2023.05.31.541819},\n\tabstract = {Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fates\nin vitro\noften relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards an\nin vitro\nmorphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.},\n\turldate = {2024-07-22},\n\tjournal = {bioRxiv},\n\tauthor = {Amin, Neal D. and Kelley, Kevin W. and Hao, Jin and Miura, Yuki and Narazaki, Genta and Li, Tommy and McQueen, Patrick and Kulkarni, Shravanti and Pavlov, Sergey and Paşca, Sergiu P.},\n\tmonth = jun,\n\tyear = {2023},\n\tpmid = {37398073},\n\tpmcid = {PMC10312596},\n\tkeywords = {Collection: Brain Organoids},\n\tpages = {2023.05.31.541819},\n}\n\n\n\n","author_short":["Amin, N. D.","Kelley, K. W.","Hao, J.","Miura, Y.","Narazaki, G.","Li, T.","McQueen, P.","Kulkarni, S.","Pavlov, S.","Paşca, S. P."],"key":"amin_generating_2023","id":"amin_generating_2023","bibbaseid":"amin-kelley-hao-miura-narazaki-li-mcqueen-kulkarni-etal-generatinghumanneuraldiversitywithamultiplexedmorphogenscreeninorganoids-2023","role":"author","urls":{"Paper":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312596/"},"keyword":["Collection: Brain Organoids"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/zotero/XiangrongLu","dataSources":["qNt3P6iaAg3Ryeo4C"],"keywords":["collection: brain organoids"],"search_terms":["generating","human","neural","diversity","multiplexed","morphogen","screen","organoids","amin","kelley","hao","miura","narazaki","li","mcqueen","kulkarni","pavlov","paşca"],"title":"Generating human neural diversity with a multiplexed morphogen screen in organoids","year":2023}