2. Academic Validation
  3. Ribosome biogenesis is essential for hemogenic endothelial cells to generate hematopoietic stem cells

Ribosome biogenesis is essential for hemogenic endothelial cells to generate hematopoietic stem cells

  • Development. 2024 Nov 1;151(21):dev202875. doi: 10.1242/dev.202875.
Di Liu 1,  Haizhen Wang 2,  Haifeng Chen 3,  Xitong Tian 4 5,  Yuqing Jiao 4,  Chi Wang 6,  Yuhui Li 6,  Zongcheng Li 5,  Siyuan Hou 7,  Yanli Ni 5,  Bing Liu 5 6,  Yu Lan 6,  Jie Zhou 4 5
Affiliations

Affiliations

  • 1 Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing 100053, China.
  • 2 The Fifth Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, Guangdong 510900, China.
  • 3 Dermatology Hospital, Southern Medical University, Guangzhou 510091, China.
  • 4 Chinese PLA medical school, Chinese PLA General Hospital, Beijing 100853, China.
  • 5 State Key Laboratory of Experimental Hematology, Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
  • 6 Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China.
  • 7 Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China.
PMID: 39324287 DOI: 10.1242/dev.202875
Abstract

Undergoing endothelial-to-hematopoietic transition, a small fraction of embryonic aortic endothelial cells specializes into hemogenic endothelial cells (HECs) and eventually gives rise to hematopoietic stem cells (HSCs). Previously, we found that the activity of ribosome biogenesis (RiBi) is highly enriched in the HSC-primed HECs compared with adjacent arterial endothelial cells; however, whether RiBi is required in HECs for the generation of HSCs remains to be determined. Here, we have found that robust RiBi is markedly augmented during the endothelial-to-hematopoietic transition in mouse. Pharmacological inhibition of RiBi completely impeded the generation of HSCs in explant cultures. Moreover, disrupting RiBi selectively interrupted the HSC generation potential of HECs rather than T1 pre-HSCs, which was in line with its influence on cell cycle activity. Further investigation revealed that, upon HEC specification, the master transcription factor Runx1 dramatically bound to the loci of genes involved in RiBi, thereby facilitating this biological process. Taken together, our study provides functional evidence showing the indispensable role of RiBi in generating HSCs from HECs, providing previously unreported insights that may contribute to the improvement of HSC regeneration strategies.

Keywords

Hematopoietic stem cell development; Hemogenic endothelial cells; Mouse; Ribosome biogenesis.

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