{"id":"https://openalex.org/W4407976440","doi":"https://doi.org/10.1016/j.jtct.2025.01.468","title":"Human Lifetime Physiology Reveals an Engraftment-Enhancing Gene Expression Program","display_name":"Human Lifetime Physiology Reveals an Engraftment-Enhancing Gene Expression Program","publication_year":2025,"publication_date":"2025-02-01","ids":{"openalex":"https://openalex.org/W4407976440","doi":"https://doi.org/10.1016/j.jtct.2025.01.468"},"language":"en","primary_location":{"id":"doi:10.1016/j.jtct.2025.01.468","doi":"https://doi.org/10.1016/j.jtct.2025.01.468","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2025.01.468","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/j.jtct.2025.01.468","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5107541655","display_name":"Parker C\u00f4t\u00e9","orcid":"https://orcid.org/0000-0001-7086-0573","observed_orcids":["https://orcid.org/0000-0001-7086-0573"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Parker Cote","raw_affiliation_strings":["Pediatrics, Hematology/Oncology, UC San Diego, La Jolla, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pediatrics, Hematology/Oncology, UC San Diego, La Jolla, CA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000958616","display_name":"Michael Kuoch","orcid":"https://orcid.org/0000-0003-1229-7879","observed_orcids":["https://orcid.org/0000-0003-1229-7879"]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael Kuoch","raw_affiliation_strings":["Massachusetts Institute of Technology, Cambridge, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts Institute of Technology, Cambridge, MA","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069087536","display_name":"Jennifer Whangbo","orcid":"https://orcid.org/0000-0002-5759-2532","observed_orcids":["https://orcid.org/0000-0002-5759-2532"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jennifer Whangbo","raw_affiliation_strings":["Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Grant Rowe","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1288882113","display_name":"Boston Children's Hospital","ror":"https://ror.org/00dvg7y05","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1288882113"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Grant Rowe","raw_affiliation_strings":["Boston Children's Hospital, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Boston Children's Hospital, Boston, MA","institution_ids":["https://openalex.org/I1288882113"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5058731290","display_name":"Hojun Li","orcid":"https://orcid.org/0000-0002-8129-0390","observed_orcids":["https://orcid.org/0000-0002-8129-0390"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]},{"id":"https://openalex.org/I4210087384","display_name":"Rady Children's Hospital-San Diego","ror":"https://ror.org/00414dg76","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087384"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Hojun Li","raw_affiliation_strings":["Pediatrics, Hematology/Oncology, UC San Diego, Rady Children's Hospital, La Jolla, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pediatrics, Hematology/Oncology, UC San Diego, Rady Children's Hospital, La Jolla, CA","institution_ids":["https://openalex.org/I36258959","https://openalex.org/I4210087384"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5058731290"],"corresponding_institution_ids":["https://openalex.org/I36258959","https://openalex.org/I4210087384"],"apc_list":{"value":3650,"currency":"USD","value_usd":3650},"apc_paid":{"value":3650,"currency":"USD","value_usd":3650},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.04154266,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"31","issue":"2","first_page":"S308","last_page":"S308"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10345","display_name":"Hematopoietic Stem Cell Transplantation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10345","display_name":"Hematopoietic Stem Cell Transplantation","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.0,"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/T10176","display_name":"Mesenchymal stem cell research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hematopoietic-engraftment","display_name":"hematopoietic engraftment","score":0.921999990940094},{"id":"https://openalex.org/keywords/transcriptional-programs","display_name":"transcriptional programs","score":0.7990000247955322},{"id":"https://openalex.org/keywords/hematopoietic-stem-and-progenitor-cells","display_name":"hematopoietic stem and progenitor cells","score":0.9459999799728394},{"id":"https://openalex.org/keywords/fetal-liver","display_name":"fetal liver","score":0.4659999907016754},{"id":"https://openalex.org/keywords/second-trimester","display_name":"second trimester","score":0.7670000195503235},{"id":"https://openalex.org/keywords/heat-shock-proteins","display_name":"heat shock proteins","score":0.746999979019165},{"id":"https://openalex.org/keywords/ap-1-transcription-factor","display_name":"AP-1 transcription factor","score":0.9819999933242798},{"id":"https://openalex.org/keywords/zinc-finger-proteins","display_name":"zinc finger proteins","score":0.8650000095367432},{"id":"https://openalex.org/keywords/mrna-stability","display_name":"mRNA stability","score":0.6579999923706055},{"id":"https://openalex.org/keywords/consensus-non-negative-matrix-factorization","display_name":"consensus non-negative matrix factorization","score":0.8410000205039978},{"id":"https://openalex.org/keywords/single-cell-rna-sequencing","display_name":"single-cell RNA sequencing","score":0.531000018119812},{"id":"https://openalex.org/keywords/xenograft-transplantation","display_name":"xenograft transplantation","score":0.6729999780654907},{"id":"https://openalex.org/keywords/graft-failure","display_name":"graft failure","score":0.4869999885559082},{"id":"https://openalex.org/keywords/sickle-cell-disease","display_name":"sickle cell disease","score":0.6700000166893005},{"id":"https://openalex.org/keywords/autologous-transplantation","display_name":"autologous transplantation","score":0.6190000176429749}],"concepts":[{"id":"https://openalex.org/C90559484","wikidata":"https://www.wikidata.org/wiki/Q778379","display_name":"Expression (computer science)","level":2,"score":0.5339898467063904},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.5313977003097534},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4915665090084076},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.44923877716064453},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.43727898597717285},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4025460183620453},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3124351501464844},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.1942252516746521},{"id":"https://openalex.org/C199360897","wikidata":"https://www.wikidata.org/wiki/Q9143","display_name":"Programming language","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1016/j.jtct.2025.01.468","doi":"https://doi.org/10.1016/j.jtct.2025.01.468","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2025.01.468","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1016/j.jtct.2025.01.468","doi":"https://doi.org/10.1016/j.jtct.2025.01.468","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2025.01.468","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Observational Study","id":"https://openalex.org/study-designs/observational-study"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4312731584","https://openalex.org/W2979653235","https://openalex.org/W2584106426","https://openalex.org/W7097787584","https://openalex.org/W4214629326","https://openalex.org/W2731013804","https://openalex.org/W4205400754","https://openalex.org/W2988525175","https://openalex.org/W4225406416","https://openalex.org/W3131018054"],"abstract_inverted_index":{"Graft":[0],"failure":[1,62],"and":[2,17,63,136,203,218,256,276,311,355,400,406],"poor":[3,64],"graft":[4,61,65],"function":[5,66],"due":[6],"to":[7,53,125,182,228,239,359,373,387,408],"insufficient":[8],"engraftment":[9,31,79,99,295,308,361,379,399,410],"have":[10,367],"high":[11,328,337],"rates":[12],"of":[13,25,40,70,78,110,178,206,245,303,324,332,396],"mortality":[14],"in":[15,85,100,114,153,161,316,347,352],"blood":[16],"marrow":[18,307,398],"transplant":[19,350],"(BMT)":[20],"patients.":[21],"Although":[22],"some":[23],"aspects":[24],"the":[26,34,41,51,73,86,91,101,127,147,179,184,301,393],"principles":[27],"governing":[28],"human":[29,172,197,246,371,382],"hematopoietic":[30,134],"are":[32,143,158,174],"known,":[33],"field":[35],"lacks":[36],"a":[37,68,106,220,375],"holistic":[38],"understanding":[39,77],"biologic":[42],"mechanisms":[43],"dictating":[44],"this":[45,120,287,314,333,388],"process.":[46],"This":[47,259],"knowledge":[48,121],"gap":[49],"limits":[50],"ability":[52],"design":[54],"rational":[55],"approaches":[56],"for":[57,75,404],"preventing":[58],"or":[59,329],"mitigating":[60],"as":[67,94],"complication":[69],"BMT.":[71],"Furthermore,":[72],"need":[74],"improved":[76],"biology":[80],"is":[81,261],"not":[82,144],"only":[83],"relevant":[84,166],"allogeneic":[87],"setting,":[88,93],"but":[89],"also":[90,356],"autologous":[92],"illustrated":[95],"by":[96,263],"markedly":[97],"delayed":[98],"first":[102,200,309],"patient":[103],"treated":[104],"on":[105],"recent":[107],"clinical":[108],"trial":[109],"CRISPR-mediated":[111],"gene":[112,234],"correction":[113],"sickle":[115],"cell":[116,215],"disease.":[117],"To":[118],"address":[119],"gap,":[122],"we":[123,163,366],"sought":[124],"identify":[126,231,374],"molecular":[128,394],"properties":[129,380],"that":[130,142,157,165,286],"distinguish":[131],"actively":[132,145,159,175],"engrafting":[133,160],"stem":[135],"progenitor":[137],"cells":[138,156],"(HSCPs)":[139],"from":[140,194],"those":[141],"repopulating":[146],"bone":[148,187,306,397],"marrow.":[149,188],"Given":[150],"feasibility":[151],"issues":[152],"collecting":[154],"donor":[155],"patients,":[162],"reasoned":[164],"physiology":[167,372],"occurs":[168],"during":[169,254,300],"mid-gestation,":[170,202,255],"when":[171,305],"HSCs":[173],"migrating":[176],"out":[177],"fetal":[180],"liver":[181],"engraft":[183],"newly":[185],"formed":[186],"We":[189,212,284],"collected":[190],"58,041":[191],"CD34+":[192],"HSPCs":[193,326,335],"26":[195],"independent":[196],"donors":[198],"spanning":[199],"trimester,":[201],"every":[204],"decade":[205],"postnatal":[207],"life":[208,304],"through":[209],"age":[210],"77.":[211],"performed":[213],"single":[214],"RNA-sequencing":[216],"(scRNA-seq)":[217],"applied":[219],"novel":[221],"bioinformatic":[222],"approach,":[223],"consensus":[224],"non-negative":[225],"matrix":[226],"factorization,":[227],"de":[229],"novo":[230],"35":[232],"distinct":[233],"expression":[235],"programs":[236],"(GEPs)":[237],"used":[238],"varying":[240],"degrees":[241],"at":[242],"different":[243],"phases":[244],"life.":[247],"One":[248],"such":[249],"GEP":[250,260,288,376],"had":[251],"peak":[252],"utilization":[253,299,331,338,345],"none":[257],"postnatally.":[258],"defined":[262],"heat":[264],"shock":[265],"proteins,":[266],"AP-1":[267],"transcription":[268],"factors,":[269,275],"zinc":[270],"finger":[271],"protein":[272],"mRNA":[273],"stability":[274],"surface":[277],"markers":[278],"previously":[279],"associated":[280,291],"with":[281,292,327,336,362],"lymphocyte":[282],"activation.":[283],"hypothesized":[285],"would":[289],"be":[290],"higher":[293,363],"efficiency":[294],"given":[296],"it's":[297],"specific":[298],"phase":[302],"occurs,":[310],"thus":[312],"tested":[313],"hypothesis":[315],"mouse":[317],"xenograft":[318],"transplantation":[319],"assays.":[320],"Upon":[321],"FACS":[322],"isolation":[323],"mid-gestation":[325],"low":[330,344],"GEP,":[334],"engrafted":[339],"more":[340],"efficiently":[341],"than":[342],"their":[343],"counterparts":[346],"limiting":[348],"dilution":[349],"assays":[351],"NSG":[353],"mice,":[354],"gave":[357],"rise":[358],"multi-potent":[360],"frequency.":[364],"Thus,":[365],"leveraged":[368],"naturally":[369],"occurring":[370],"conferring":[377],"efficient":[378],"upon":[381],"HSPCs.":[383],"The":[384],"genes":[385],"contributing":[386],"program":[389],"provide":[390],"insight":[391],"into":[392],"drivers":[395],"represent":[401],"candidate":[402],"targets":[403],"intervention":[405],"augmentation":[407],"prevent":[409],"failure.":[411]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2025-02-27T00:00:00"}