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Recapitulative haematopoietic development of human pluripotent stem cells in the absence of exogenous haematopoietic cytokines |
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| Authors: | Elena S. Philonenko Ying Tan Cuihua Wang Baoyun Zhang Zahir Shah Jianguang Zhang Hanif Ullah Sergei L. Kiselev Maria A. Lagarkova Dandan Li Yong Dai Igor M. Samokhvalov |
| Affiliation: | 1. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;2. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China University of Chinese Academy of Sciences, Beijing, China Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (equal), Investigation (lead), Methodology (lead), Visualization (equal), Writing - review & editing (equal);3. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China Contribution: Data curation (supporting), Formal analysis (equal), Investigation (equal), Methodology (equal), Resources (supporting), Software (lead), Validation (supporting), Visualization (equal);4. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China Contribution: Investigation (equal), Methodology (equal), Resources (equal), Validation (supporting), Writing - review & editing (supporting);5. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China University of Chinese Academy of Sciences, Beijing, China Contribution: Formal analysis (supporting), Investigation (equal), Methodology (equal), Software (supporting), Validation (supporting);6. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China Contribution: Investigation (equal), Methodology (equal), Visualization (supporting);7. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China University of Chinese Academy of Sciences, Beijing, China Contribution: Investigation (equal), Methodology (equal);8. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia Contribution: Resources (equal), Supervision (supporting), Writing - review & editing (supporting);9. Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia Contribution: Resources (equal), Supervision (supporting), Writing - review & editing (supporting);10. Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Diseases and Precision Medicine, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern, University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen, China Contribution: Funding acquisition (supporting), Resources (equal);11. Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Diseases and Precision Medicine, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern, University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen, China |
| Abstract: | To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. The removal of cytokines revealed a broad developmental potential of the early blood cells, stabilized the hPSC-derived definitive precursors and led to spontaneous activation of inflammatory signalling. Our cytokine-free protocol is simple, efficient, reproducible and applicable for embryonic stem cells (ESCs) and induced PSCs. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying the early human haematopoietic development. |
| Keywords: | haematopoiesis haematopoietic stem cells human haematopoietic development human pluripotent stem cells inflammation |