Human yolk sac-derived innate lymphoid-biased multipotent progenitors emerge prior to hematopoietic stem cell formation,Developmental Cell

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Human yolk sac-derived innate lymphoid-biased multipotent progenitors emerge prior to hematopoietic stem cell formation
Developmental Cell ( IF 10.7 ) Pub Date : 2024-07-11 , DOI: 10.1016/j.devcel.2024.06.010
Yanli Ni ₁ , Guoju You ₂ , Yandong Gong ₁ , Xiaoyu Su ₃ , Yuan Du ₄ , Xiaoshuang Wang ₅ , Xiaochen Ding ₁ , Qingfeng Fu ₁ , Man Zhang ₁ , Tao Cheng ₆ , Yu Lan ₇ , Bing Liu ₈ , Chen Liu ₉

Affiliation

State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Senior Department of Hematology, Fifth Medical Center, Medical Innovation Research Department, Chinese PLA General Hospital, Beijing 100071, China.
School of Medicine, Tsinghua University, Beijing 100080, China.
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212013, China.
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650031, China.
Department of Biochemistry and Molecular Biology, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Department of Biochemistry and Molecular Biology, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; Tianjin Institutes of Health Science, Tianjin 301600, China.
State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China.
State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Senior Department of Hematology, Fifth Medical Center, Medical Innovation Research Department, Chinese PLA General Hospital, Beijing 100071, China; State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650031, China; Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we demonstrated the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB, and IRF8 at Carnegie stage 10, much earlier than the first HSC emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in the yolk sac than the embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP to differentiate into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSC seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs. Overall, our data identified the origin, potential, and migratory dynamics of innate lymphoid-biased multipotent progenitors in human yolk sac before HSC emergence, providing insights for understanding the stepwise establishment of innate immune system in humans.

中文翻译：

人卵黄囊来源的先天性淋巴偏向多能祖细胞在造血干细胞形成之前出现

造血干细胞（HSC）非依赖性淋巴细胞生成已在小鼠胚胎中阐明。然而，我们对人类胚胎对应物的理解仍然有限。在这里，我们证明了在卡内基第 10 阶段存在表达 CD34、IL7R、LTB 和 IRF8 的人卵黄囊衍生的淋巴偏向祖细胞（YSLP），远早于第一次 HSC 出现。在这个早期阶段，这些祖细胞在卵黄囊中的数量和淋巴细胞潜能都显著高于胚胎本身。重要的是，单细胞/大量培养和 CITE-seq 阐明了 YSLP 分化为先天淋巴细胞和树突状细胞的趋势。值得注意的是，HSC 接种前后胎儿肝脏中的淋巴祖细胞表现出明显的转录特征，前者与 YSLPs 非常相似。总体而言，我们的数据确定了 HSC 出现前人卵黄囊中先天性淋巴偏向多能祖细胞的起源、潜力和迁移动力学，为了解人类先天免疫系统的逐步建立提供了见解。

更新日期：2024-07-11

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