Identification and characterization of human hematopoietic mesoderm  

作　　者：Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou 

机构地区：[1]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,China [2]Tianjin Institutes of Health Science,Tianjin 301600,China [3]CAMS Center for Stem Cell Medicine,PUMC Department of Stem Cell and Regenerative Medicine,Tianjin 300020,China [4]Division of Cell,Developmental and Integrative Biology,School of Medicine,South China University of Technology,Guangzhou 510006,China

出　　处：《Science China(Life Sciences)》2024年第2期320-331,共12页中国科学（生命科学英文版）

基　　金：supported by the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-073,2021-I2M-1-040,2022-I2M-JB-015);the National Key Research and Development Program of China(2021YFA1100703,2021YFA1103000);Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00031);the National Natural Science Foundation of China(82125003,32271161,82200141);Tianjin Municipal Science and Technology Commission Grant(20JCYBJC00240,22ZXSYSY00010,22JCQNJC01270)。

摘　　要：The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic lineages.We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells.Mechanistically,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its enhancer.Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation.In conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关 键 词：hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1 

分 类 号：R331[医药卫生—人体生理学]