the core of this atlas consists of a fully integrated healthy reference of 14 datasets with 61 cell identities, including rare and novel cell types, representing a data - derived consensus annotation of the cellular landscape of the human lung. we leveraged the unprecedented complexity of the hlca to recover cell type - specific gene modules associated with covariates such as lung anatomical location, age, sex, bmi and smoking status. by projecting data onto the hlca, we showed that the hlca enables a fast and detailed annotation of new datasets, as well as the identification of unique, disease-associated cell states and cell states common to multiple diseases. the hlca is publicly available as a resource for the community, together with an online platform for automate d mapping of new data. taken together, the hlca is a universal reference for single - cell lung research that promises to accelerate future studies into pulmonary health and disease. the ultimate goal of a human lung cell atlas reference is to provide a comprehensive overview of all cells in the healthy human lung, as well as their variation from individual to individual. despite its overall diversity, the hlca is limited by the biological, demographic and experimental diversity in the foundational single - cell studies. for example, 65 % of the hlca core data are from individuals of european harmonized ethnicity, highlighting the urgent need for diversification of the population sampled in lung studies. moreover, ethnicity metadata were based on self - reports and harmonized across datasets, which is an imperfect approach to representing the diversity of the atlas. snp - based inference of genetic ancestry constitutes a more objective and therefore preferable approach to the grouping of individuals based on genetic background and would aid in better assessing the genetic diversity captured in the atlas. overall, more diverse samples will enrich the atlas, diversify captured cell identities and improve the quality of the hlca as a reference for new datasets. such a reference will also enable comparison with model systems such as mice, cell lines or organoids, although further method development may be required to map across diverse in vitro and clinical datasets. the constituent datasets of the hlca vary widely in experimental design, such as the sample handling protocol or single - cell platform used, causing dataset - specific batch effects. the quality of the hlca hinges on the choice of data integration method, with methods such as seurat ’ s rpca and harmony failing to correctly group rare cell identities into separate clusters. nevertheless, also in the hlca, certain subsets of t cells ( regulatory t cells and γδ t cells ) could not be identified as separate clusters, showing the limitations of the current hlca in capturing cellular heterogeneity for a subset of immune cell types. mapping additional datasets with high - resolution annotations ( for example, derived from multimodal data ) could provide the power to detect these cell identities in the atlas. indeed, the hlca must be viewed as a live resource that requires continuous updates. while we showed that mapping new, spatially annotate d data to the hlca core can refine hlca annotations, this new knowledge must be consolidated by regular updates of the hlca with new datasets ( including epigenomic, spatial and imaging data ) and refinements of hlca annotations based on additional expert opinions. thereby, the hlca can serve as a community - and data - driven platform for open discussion on lung cell identities as the respiratory community progresses in charting the cellular landscape of the lung. in this process, we envision that the hlca will be completed in two phases: first on the level of cellular variation ( when no new consensus cell types can be found ) and then in the description of individual variation ( when population diversity is fully represented ). taken together, the hlca provides a central single - cell reference of unprecedented size. it offers a model framework for building integrated, consensus - based, population - scale atlases for other organs within the human cell atlas. the hlca is publicly available, and combined with an open - access platform to map new datasets to the atlas, this resource paves the way toward a better and more complete understanding of both health and disease in the human lung. ethics approval information per study was as follows. for the pooled data from refs., approval was given by the vanderbilt institutional review board ( irb ) ( numbers 060165 and 171657 ) and western irb ( number 20181836 ). all samples were collected from declined organ donors who were also consented for research. the study was approved by the comite de protection des personnes sud est iv ( approval number 17 / 081 ). informed written consent was obtained from all participants involved. for jain _ misharin _ 2021 ( a. v. m., m. j. and n. s. m., newly generated dataset ), the protocol was approved by the northwestern university irb ( stu00214826 ). written informed consent was obtained from all study participants. patient tissues were obtained under a protocol approved by stanford university ’ s human subjects research compliance office ( irb 15166 ). informed consent was obtained from each patient before surgery. healthy control lungs were obtained under a protocol approved by the university of pittsburgh committee for oversight of research and clinical training involving decedents ( corid protocol 718 ) and following rejection as candidate donors for transplant ( irb study 19100326 ). tissue samples were obtained from the cambridge biorepository for translational medicine ( cbtm ) with approval from the national research ethics services ( nres ) committee of east of england — cambridge south ( 15 / ee / 0152 ). tissue samples were obtained with informed consent from the donor families. the protocol was approved by the northwestern university irb ( stu00212120 ). written informed consent was obtained from all individuals in the study. for the pooled data from ref. and associated unpublished data, the protocol was approved by the irb ( algemeen beoordelings - en registratieformulier number nl69765. 042. 19 ). the national jewish health irb approved the research under irb protocols hs - 3209 and hs - 2240. informed consent was obtained from authorized family members of all donors. approval was given by the nres committee of east of england — cambridge south ( research ethics committee ( rec ) reference: 15 / ee / 0152 ). informed consent for use of the tissue was obtained from the donors ’ families. for barbry _ unpubl ( p. b., l. - e. z., m. j. a., a. c., c. b. et al., newly generated dataset ), the protocol was approved by the centre hospitalier universitaire de nice. nasal and tracheobronchial samples were collected from patients with ipf after obtaining their informed consent. approved was given by the irb of northwestern university ( stu00212120, stu00213177, stu00212511 and stu00212579 ). for inclusion in this study, patients or their designated medical power of attorney provided informed consent. for duong _ lungmap _ unpubl ( t. e. d., k. z., x. s., j. s. h. and g. p., newly generated dataset ), all postmortem human donor lung samples were obtained from the biorepository for investigation of neonatal diseases of the lung ( brindl ), supported by the national heart, lung, and blood institute ( nhlbi ) lungmap human tissue core housed at the university of rochester. consent can be found on the repository ’ s website ( brindl. urmc. rochester. edu / ). the study was conducted in accordance with the declaration of helsinki and department of health and human services belmont report. the use of biomaterial and data for this study was approved by the local ethics committee of the medical faculty heidelberg ( s - 270 / 2001 and s - 538 / 2012 ).