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Identification and characterization of human hematopoietic mesoderm

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Abstract

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.

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Acknowledgement

This work was 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) and Tianjin Municipal Science and Technology Commission Grant (20JCYBJC00240, 22ZXSYSY00010, 22JCQNJC01270). We thank Dr. Shankar Srinivas and Baoyang Hu for providing the single-cell profiling data from human embryos or materials for this study. We thank Dr. Daniel Ackerman (Insight Editing London) for editing the manuscript during preparation.

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Authors and Affiliations

  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

    Yuqi Wen, Jingjing Zhao, Runqing Zhang, Fan Liu, Xiaoyuan Chen, Dan Wu, Mengge Wang, Cuicui Liu, Pei Su, Xin Gao, Lu Wang, Hongtao Wang & Jiaxi Zhou

  2. Tianjin Institutes of Health Science, Tianjin, 301600, China

    Yuqi Wen, Jingjing Zhao, Runqing Zhang, Fan Liu, Xiaoyuan Chen, Dan Wu, Mengge Wang, Cuicui Liu, Pei Su, Xin Gao, Lu Wang, Hongtao Wang & Jiaxi Zhou

  3. CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, 300020, China

    Yuqi Wen, Jingjing Zhao, Runqing Zhang, Fan Liu, Xiaoyuan Chen, Dan Wu, Mengge Wang, Cuicui Liu, Pei Su, Xin Gao, Lu Wang, Hongtao Wang & Jiaxi Zhou

  4. Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Panpan Meng & Yiyue Zhang

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  1. Yuqi Wen
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Correspondence to Hongtao Wang or Jiaxi Zhou.

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Wen, Y., Zhao, J., Zhang, R. et al. Identification and characterization of human hematopoietic mesoderm. Sci. China Life Sci. 67, 320–331 (2024). https://doi.org/10.1007/s11427-022-2374-x

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