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轴在人多能干细胞向内皮细胞到造血细胞的转变过程中调节谱系定向。

axis regulates lineage commitment during endothelial-to-hematopoietic transition from human pluripotent stem cells.

作者信息

Qu Kengyuan, Mo Shaokang, Huang Junfeng, Liu Shan, Zhang Shuo, Shen Jun, Yen Kuangyu

机构信息

Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

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.

出版信息

iScience. 2024 Jun 28;27(8):110409. doi: 10.1016/j.isci.2024.110409. eCollection 2024 Aug 16.

DOI:10.1016/j.isci.2024.110409
PMID:39108738
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11301078/
Abstract

PU.1 () is pivotal in hematopoiesis, yet its role in human endothelial-to-hematopoietic transition (EHT) remains unclear. Comparing human and EHT transcriptomes revealed 's regulatory role. Knocking down during EHT led to a decrease in the generation of hematopoietic progenitor cells (HPCs) and their differentiation potential. Through multi-omic analysis, we identified and - transcription factors specific to erythroid/myeloid and lymphoid cells, respectively - as downstream targets of . Overexpressing or partially rescues the knockdown-induced reduction in HPC formation. Specifically, overexpression restores myeloid lineage potential, while overexpression re-establishes lymphoid lineage potential. We also observed a - axis in the regulatory network in EHT. Taken together, our findings shed new light on the role of in regulating lineage commitment during EHT, potentially contributing to the heterogeneity of hematopoietic stem cells (HSCs).

摘要

PU.1（）在造血过程中起关键作用，但其在人类内皮细胞向造血细胞转变（EHT）中的作用仍不清楚。比较人类和EHT转录组揭示了的调节作用。在EHT期间敲低导致造血祖细胞（HPC）的生成及其分化潜能下降。通过多组学分析，我们分别确定了红系/髓系细胞和淋巴系细胞特有的转录因子和 - 作为的下游靶点。过表达或部分挽救了敲低诱导的HPC形成减少。具体而言，过表达恢复了髓系谱系潜能，而过表达重新建立了淋巴系谱系潜能。我们还在EHT的调节网络中观察到一个 - 轴。综上所述，我们的研究结果为在EHT期间调节谱系定向中的作用提供了新的线索，可能有助于造血干细胞（HSC）的异质性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/fcf85ff134ce/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/05c7809497b5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/76740bc85d66/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/73dd2bad304f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/32314b284269/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/51e68bbf7a9b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/c4a2bf2d38b8/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/93afc7e52b19/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/1113f56fd991/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/fcf85ff134ce/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/05c7809497b5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/76740bc85d66/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/73dd2bad304f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/32314b284269/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/51e68bbf7a9b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/c4a2bf2d38b8/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/93afc7e52b19/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/1113f56fd991/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f043/11301078/fcf85ff134ce/gr8.jpg

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