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Here, we constructed a high-resolution landscape of the entire hematopoietic system by integrating transcriptomes of \u223c1 million cells from 207 healthy samples spanning five developmental stages (fetal, neonatal, childhood, adult, and elderly), and identified 96 blood cell clusters, including a VNN2-marked monocyte subset in the fetus and TSHZ2-marked T cell subsets exhibiting distinct age-dependent dynamics. We uncovered a reversal in hematopoietic stem cell\/multipotent progenitor (HSC\/MPP) stemness around childhood and a postnatal lymphoid bias shift from reduced early B\/T lineage potential to enhanced natural killer (NK) cytotoxicity, coordinately orchestrated by intracellular transcription factor activity and intercellular interactions. Projecting 116 pan-malignancy samples (9 hematological malignancies) to our refined blood cell reference, we identified the upregulation of MYC and MHC II signaling as relatively conserved features correlating with poor prognosis, while hematopoiesis-related modules exhibited subtype-specific distributions with divergent clinical implications. Importantly, we developed a prognostic framework incorporating two core signatures shared across hematological malignancies and subtype-specific features. We further revealed an antagonism between inflammatory and cytotoxic programs across malignancies. Together, we established a panoramic landscape of the human hematopoietic system and elaborated its lifelong behaviors, in which a steady-state reference enabled the delineation of pathological hallmarks across hematological malignancies.<\/jats:p>","DOI":"10.1093\/procel\/pwag064","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:33:16Z","timestamp":1788867196000},"source":"Crossref","is-referenced-by-count":0,"title":["The lifelong transcriptomic landscape of human blood cells"],"prefix":"10.1093","author":[{"given":"Xiaowei","family":"Xie","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianshuo","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojin","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou 510060,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiming","family":"Pang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changya","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 301600,","place":["China"]},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University , Tianjin 300070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4521-7524","authenticated-orcid":false,"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020,","place":["China"]},{"name":"Tianjin Institutes of Health Science , Tianjin 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