{"id":"https://openalex.org/W7213467145","doi":"https://doi.org/10.64898/2026.09.14.751550","title":"Differentiation protocol and maturation shape the axial identity and synaptic state in human iPSC-derived spinal motor neurons","display_name":"Differentiation protocol and maturation shape the axial identity and synaptic state in human iPSC-derived spinal motor neurons","publication_year":2026,"publication_date":"2026-09-17","ids":{"openalex":"https://openalex.org/W7213467145","doi":"https://doi.org/10.64898/2026.09.14.751550"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.14.751550","doi":"https://doi.org/10.64898/2026.09.14.751550","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751550","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751550.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751550.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5017913627","display_name":"Alba Sansa","orcid":"https://orcid.org/0000-0001-5347-6262","observed_orcids":["https://orcid.org/0000-0001-5347-6262"]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alba Sansa","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074925454","display_name":"Vladimir Zhemkov","orcid":"https://orcid.org/0000-0002-6554-1938","observed_orcids":["https://orcid.org/0000-0002-6554-1938"]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vladimir A Zhemkov","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037924144","display_name":"Monica Feole","orcid":"https://orcid.org/0000-0002-7951-7234","observed_orcids":["https://orcid.org/0000-0002-7951-7234"]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Monica Feole","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112632833","display_name":"Jaquelyn M. Villalba","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jaquelyn M Villalba","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110326079","display_name":"Shaughn Bell","orcid":"https://orcid.org/0000-0002-3621-636X","observed_orcids":["https://orcid.org/0000-0002-3621-636X"]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shaughn Bell","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5076105306","display_name":"Clive N. Svendsen","orcid":"https://orcid.org/0000-0001-8696-3446","observed_orcids":["https://orcid.org/0000-0001-8696-3446"]},"institutions":[{"id":"https://openalex.org/I1282927834","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1282927834"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Clive N Svendsen","raw_affiliation_strings":["Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cedars-Sinai Board of Governors Regenerative Medicine Institute, Los Angeles, CA, USA","institution_ids":["https://openalex.org/I1282927834"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5076105306"],"corresponding_institution_ids":["https://openalex.org/I1282927834"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10608","display_name":"Neurogenesis and neuroplasticity mechanisms","score":0.0013000000035390258,"subfield":{"id":"https://openalex.org/subfields/2806","display_name":"Developmental Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10268","display_name":"Developmental Biology and Gene Regulation","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ipsc-derived-motor-neurons","display_name":"iPSC-derived motor neurons","score":0.8100000023841858},{"id":"https://openalex.org/keywords/spinal-motoneurons","display_name":"spinal motoneurons","score":0.8889999985694885},{"id":"https://openalex.org/keywords/motor-neuron-differentiation","display_name":"motor neuron differentiation","score":0.5879999995231628},{"id":"https://openalex.org/keywords/synaptic-maturation","display_name":"synapse maturation","score":0.7419999837875366},{"id":"https://openalex.org/keywords/acetylcholine-receptor","display_name":"acetylcholine receptor","score":0.6959999799728394},{"id":"https://openalex.org/keywords/neurite-branching","display_name":"neurite branching","score":0.6909999847412109},{"id":"https://openalex.org/keywords/microfluidic-co-culture","display_name":"microfluidic co-culture","score":0.8019999861717224}],"concepts":[{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.8112000226974487},{"id":"https://openalex.org/C2776752467","wikidata":"https://www.wikidata.org/wiki/Q1133903","display_name":"Motor neuron","level":3,"score":0.76419997215271},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5789999961853027},{"id":"https://openalex.org/C22885893","wikidata":"https://www.wikidata.org/wiki/Q4862743","display_name":"Cholinergic","level":2,"score":0.5544000267982483},{"id":"https://openalex.org/C113246987","wikidata":"https://www.wikidata.org/wiki/Q1534415","display_name":"Neurite","level":3,"score":0.5424000024795532},{"id":"https://openalex.org/C104966671","wikidata":"https://www.wikidata.org/wiki/Q12167532","display_name":"Cholinergic neuron","level":3,"score":0.5356000065803528},{"id":"https://openalex.org/C107459253","wikidata":"https://www.wikidata.org/wiki/Q674925","display_name":"Induced pluripotent stem cell","level":4,"score":0.39959999918937683},{"id":"https://openalex.org/C2778794669","wikidata":"https://www.wikidata.org/wiki/Q43054","display_name":"Neuron","level":2,"score":0.39160001277923584},{"id":"https://openalex.org/C2780775167","wikidata":"https://www.wikidata.org/wiki/Q9606","display_name":"Spinal cord","level":2,"score":0.35839998722076416},{"id":"https://openalex.org/C94487597","wikidata":"https://www.wikidata.org/wiki/Q11101","display_name":"Sensory system","level":2,"score":0.33329999446868896},{"id":"https://openalex.org/C136834591","wikidata":"https://www.wikidata.org/wiki/Q2944097","display_name":"Neural stem cell","level":3,"score":0.33090001344680786},{"id":"https://openalex.org/C2778373776","wikidata":"https://www.wikidata.org/wiki/Q18696","display_name":"Motor cortex","level":3,"score":0.32499998807907104},{"id":"https://openalex.org/C2780196419","wikidata":"https://www.wikidata.org/wiki/Q1762173","display_name":"Nerve net","level":2,"score":0.3199999928474426},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.31049999594688416},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.301800012588501},{"id":"https://openalex.org/C171139928","wikidata":"https://www.wikidata.org/wiki/Q2915553","display_name":"Motor system","level":2,"score":0.29319998621940613},{"id":"https://openalex.org/C2775910092","wikidata":"https://www.wikidata.org/wiki/Q180623","display_name":"Acetylcholine","level":2,"score":0.29120001196861267},{"id":"https://openalex.org/C2778944004","wikidata":"https://www.wikidata.org/wiki/Q91703","display_name":"Caenorhabditis elegans","level":3,"score":0.2858999967575073},{"id":"https://openalex.org/C2780385302","wikidata":"https://www.wikidata.org/wiki/Q367158","display_name":"Protocol (science)","level":3,"score":0.2840000092983246},{"id":"https://openalex.org/C61174792","wikidata":"https://www.wikidata.org/wiki/Q420510","display_name":"Glutamate receptor","level":3,"score":0.2727999985218048},{"id":"https://openalex.org/C2778355321","wikidata":"https://www.wikidata.org/wiki/Q17079427","display_name":"Identity (music)","level":2,"score":0.2680000066757202},{"id":"https://openalex.org/C185263204","wikidata":"https://www.wikidata.org/wiki/Q1154774","display_name":"Electrophysiology","level":2,"score":0.2651999890804291},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.2624000012874603},{"id":"https://openalex.org/C545706735","wikidata":"https://www.wikidata.org/wiki/Q9404","display_name":"Nervous system","level":2,"score":0.260699987411499},{"id":"https://openalex.org/C200707615","wikidata":"https://www.wikidata.org/wiki/Q13652744","display_name":"Neuroepithelial cell","level":4,"score":0.2567000091075897},{"id":"https://openalex.org/C2776219046","wikidata":"https://www.wikidata.org/wiki/Q162657","display_name":"Neurotransmitter","level":3,"score":0.25440001487731934},{"id":"https://openalex.org/C200170125","wikidata":"https://www.wikidata.org/wiki/Q969316","display_name":"Neurotransmission","level":3,"score":0.25200000405311584},{"id":"https://openalex.org/C2778558090","wikidata":"https://www.wikidata.org/wiki/Q580290","display_name":"Spinal muscular atrophy","level":3,"score":0.2502000033855438}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.14.751550","doi":"https://doi.org/10.64898/2026.09.14.751550","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751550","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751550.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.14.751550","doi":"https://doi.org/10.64898/2026.09.14.751550","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751550","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751550.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.8048999905586243,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G5500107768","display_name":"CIRM Training Program in Translational Regenerative Medicine","funder_award_id":"EDUC4-12751","funder_id":"https://openalex.org/F4320306171","funder_display_name":"California Institute for Regenerative Medicine"}],"funders":[{"id":"https://openalex.org/F4320306171","display_name":"California Institute for Regenerative Medicine","ror":"https://ror.org/033m8b439"},{"id":"https://openalex.org/F4320313996","display_name":"Cedars-Sinai Medical Center","ror":"https://ror.org/02pammg90"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213467145.pdf","grobid_xml":"https://content.openalex.org/works/W7213467145.grobid-xml"},"referenced_works_count":34,"referenced_works":["https://openalex.org/W1774217609","https://openalex.org/W1973956721","https://openalex.org/W1977374662","https://openalex.org/W2037991731","https://openalex.org/W2061144812","https://openalex.org/W2094603776","https://openalex.org/W2122980330","https://openalex.org/W2137935662","https://openalex.org/W2145492799","https://openalex.org/W2169026620","https://openalex.org/W2317226401","https://openalex.org/W2766330765","https://openalex.org/W2773637439","https://openalex.org/W3001393877","https://openalex.org/W3023268851","https://openalex.org/W3037806345","https://openalex.org/W3043174733","https://openalex.org/W3115819913","https://openalex.org/W3164098570","https://openalex.org/W3178295395","https://openalex.org/W3212352454","https://openalex.org/W4210469056","https://openalex.org/W4225996888","https://openalex.org/W4296036674","https://openalex.org/W4319598353","https://openalex.org/W4319728675","https://openalex.org/W4362641064","https://openalex.org/W4366823419","https://openalex.org/W4395676185","https://openalex.org/W4401510135","https://openalex.org/W4411581365","https://openalex.org/W4415058019","https://openalex.org/W7162870851","https://openalex.org/W7172435670"],"related_works":["https://openalex.org/W4414484686","https://openalex.org/W4381615411","https://openalex.org/W2093994917","https://openalex.org/W4312039639","https://openalex.org/W4313557508","https://openalex.org/W3023268851","https://openalex.org/W2061144812","https://openalex.org/W4238297451","https://openalex.org/W4301750218","https://openalex.org/W2126493828"],"abstract_inverted_index":{"Abstract":[0],"Human":[1],"induced":[2],"pluripotent":[3],"stem":[4],"cell":[5],"(iPSC)-derived":[6],"motor":[7,21,50,89,188],"neurons":[8,22],"are":[9],"widely":[10],"used":[11],"for":[12,45,68,198],"disease":[13],"modeling.":[14],"Stem":[15],"cells":[16],"can":[17,30],"be":[18],"differentiated":[19],"into":[20,49],"by":[23],"exposure":[24],"to":[25,110,170],"specific":[26],"patterning":[27],"morphogens,":[28],"which":[29],"ultimately":[31],"determine":[32],"terminal":[33],"cellular":[34],"composition":[35],"and":[36,58,98,101,123,137,140,145,162,175,181,202],"developmental":[37],"state.":[38],"We":[39],"compared":[40,169],"two":[41],"small":[42],"molecule":[43],"workflows":[44],"human":[46,185],"iPSC":[47],"maturation":[48,72,114,176],"neurons:":[51],"a":[52,149],"rapid":[53],"direct":[54],"protocol":[55,61,77,84,109],"(diMN":[56],"protocol)":[57],"an":[59],"extended":[60],"(purMN":[62],"protocol),":[63],"with":[64,87,135,143],"both":[65],"protocols":[66],"matched":[67],"20":[69],"days":[70,112],"in":[71,113],"medium.":[73],"While":[74],"the":[75,82,107,179,193],"diMN":[76,133],"generated":[78],"mixed":[79],"neural":[80],"cultures,":[81],"purMN":[83,108,141],"provided":[85],"cultures":[86,116,134,142,190],"greater":[88],"neuron":[90,189],"enrichment,":[91],"stronger":[92],"caudal":[93],"spinal":[94,144,187],"identity,":[95],"broader":[96],"synaptic":[97],"cholinergic":[99,124],"programs,":[100],"reduced":[102],"progenitor-associated":[103,138],"signatures.":[104],"By":[105],"extending":[106],"32":[111],"media,":[115],"developed":[117],"reinforced":[118],"spinal,":[119],"postsynaptic,":[120],"presynaptic,":[121],"calcium-signaling,":[122],"features.":[125],"Across":[126],"four":[127],"independent":[128],"reference":[129],"frameworks,":[130],"deconvolution":[131],"aligned":[132],"anterior":[136],"states":[139],"post-mitotic":[146],"states.":[147],"In":[148],"microfluidic":[150],"co-culture":[151],"system,":[152],"purMNs":[153],"formed":[154],"denser,":[155],"more":[156,164],"highly":[157],"branched":[158],"distal":[159],"neurite":[160],"networks":[161],"produced":[163],"innervated":[165],"acetylcholine":[166],"receptor":[167],"clusters":[168],"diMNs.":[171],"Revealing":[172],"how":[173],"purity":[174],"jointly":[177],"define":[178],"transcriptomic":[180],"structural":[182],"state":[183],"of":[184,200],"iPSC-derived":[186],"will":[191],"help":[192],"field":[194],"choose":[195],"optimal":[196],"models":[197],"studies":[199],"neurodevelopment":[201],"neurodegenerative":[203],"diseases.":[204]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2026-09-17T00:00:00"}