CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment

Kuiying Ma; Xuan Wang; Linjie Wu; Lingling Yu; Jinhui Ye; Xueling Li; Lili Geng; Zhongyu Shi; Huihui Yang; Xijuan Zhang; Yongjian Zhang; Shuchang Wu; Pengfei Yuan; Yingchi Zhang; Fang Dong; Sha Hao; Linping Hu; Wensheng Wei; Riguo Fang; Tao Cheng

doi:10.1016/j.isci.2023.108561

CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment

iScience. 2023 Nov 24;26(12):108561. doi: 10.1016/j.isci.2023.108561. eCollection 2023 Dec 15.

Authors

Kuiying Ma¹, Xuan Wang^{2

3}, Linjie Wu^{2

3}, Lingling Yu¹, Jinhui Ye^{2

3}, Xueling Li^{2

3}, Lili Geng¹, Zhongyu Shi¹, Huihui Yang¹, Xijuan Zhang¹, Yongjian Zhang¹, Shuchang Wu¹, Pengfei Yuan¹, Yingchi Zhang^{2

3}, Fang Dong^{2

3}, Sha Hao^{2

3}, Linping Hu^{2

3}, Wensheng Wei⁴, Riguo Fang¹, Tao Cheng^{2

5

6

3}

Affiliations

¹ EdiGene Inc., Life Science Park, Changping District, Beijing 102206, China.
² 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.
³ Tianjin Institutes of Health Science, Tianjin 301600, China.
⁴ Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
⁵ Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin 300000, China.
⁶ Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin 300000, China.

Abstract

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e⁺ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e^- cells. CD66e⁺CD34⁺CD90⁺CD45RA^- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e^-CD34⁺CD90⁺CD45RA^-cells. CD66e expression also identified almost all repopulating HSCs within the CD34⁺CD90⁺CD45RA^- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Keywords: Cell biology; Omics; Stem cells research.