Integrating Spatial Transcriptomics and Single-Cell RNA-seq Reveals the Gene Expression Profling of the Human Embryonic Liver.

Xianliang Hou, Yane Yang, Ping Li, Zhipeng Zeng, Wenlong Hu, Ruilian Zhe, Xinqiong Liu, Donge Tang, Minglin Ou, Yong Dai
Author Information
  1. Xianliang Hou: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  2. Yane Yang: Shenzhen Far-East Women & Children Hospital, Shenzhen, China.
  3. Ping Li: Shenzhen Far-East Women & Children Hospital, Shenzhen, China.
  4. Zhipeng Zeng: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  5. Wenlong Hu: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  6. Ruilian Zhe: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  7. Xinqiong Liu: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  8. Donge Tang: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
  9. Minglin Ou: Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
  10. Yong Dai: Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.

Abstract

The liver is one of vital organs of the human body, and it plays an important role in the metabolism and detoxification. Moreover, fetal liver is one of the hematopoietic places during ontogeny. Understanding how this complex organ develops during embryogenesis will yield insights into how functional liver replacement tissue can be engineered and how liver regeneration can be promoted. Here, we combine the advantages of single-cell RNA sequencing and Spatial Transcriptomics (ST) technology for unbiased analysis of fetal livers over developmental time from 8 post-conception weeks (PCW) and 17 PCW in humans. We systematically identified nine cell types, and defined the developmental pathways of the major cell types. The results showed that human fetal livers experienced blood rapid growth and immigration during the period studied in our experiments, and identified the differentially expressed genes, and metabolic changes in the developmental process of erythroid cells. In addition, we focus on the expression of liver disease related genes, and found that 17 genes published and linked to liver disease mainly expressed in megakaryocyte and endothelial, hardly expressed in any other cell types. Together, our findings provide a comprehensive and clear understanding of the differentiation processes of all main cell types in the human fetal livers, which may provide reference data and information for liver disease treatment and liver regeneration.

Keywords

References

  1. Science. 2016 Jul 1;353(6294):78-82 [PMID: 27365449]
  2. Development. 2017 Jul 1;144(13):2323-2337 [PMID: 28676567]
  3. Cell Stem Cell. 2014 Sep 4;15(3):326-339 [PMID: 25017721]
  4. World J Gastroenterol. 2017 Nov 21;23(43):7666-7677 [PMID: 29209108]
  5. Nature. 2013 Aug 29;500(7464):593-7 [PMID: 23892778]
  6. Bioinformatics. 2018 Jun 1;34(11):1966-1968 [PMID: 29360929]
  7. Blood Adv. 2018 Mar 13;2(5):470-480 [PMID: 29490978]
  8. Eur J Immunol. 2005 Oct;35(10):2970-81 [PMID: 16163670]
  9. Nat Protoc. 2018 Nov;13(11):2501-2534 [PMID: 30353172]
  10. Sci Rep. 2017 Oct 11;7(1):12941 [PMID: 29021611]
  11. Development. 2019 Jun 12;146(12): [PMID: 31142540]
  12. PLoS Biol. 2019 Feb 21;17(2):e3000152 [PMID: 30789893]
  13. Bioinformatics. 2015 Jan 15;31(2):166-9 [PMID: 25260700]
  14. Nature. 2019 Oct;574(7778):365-371 [PMID: 31597962]
  15. Nat Biotechnol. 2011 Nov 13;29(12):1120-7 [PMID: 22081019]
  16. Blood Cells Mol Dis. 2013 Dec;51(4):226-31 [PMID: 24041595]
  17. Sci China Life Sci. 2018 Aug;61(8):885-892 [PMID: 29934917]
  18. Genes Immun. 2016 Apr;17(3):153-64 [PMID: 26963138]
  19. J Mol Endocrinol. 2016 Apr;56(3):R115-25 [PMID: 26887388]
  20. J Hepatol. 2004 Feb;40(2):261-8 [PMID: 14739097]
  21. Nat Methods. 2012 Mar 04;9(4):357-9 [PMID: 22388286]
  22. Nat Biotechnol. 2020 Mar;38(3):333-342 [PMID: 31932730]
  23. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  24. Nat Commun. 2018 Jun 20;9(1):2419 [PMID: 29925878]
  25. BMJ. 1990 Nov 17;301(6761):1111 [PMID: 2252919]
  26. Stat Appl Genet Mol Biol. 2005;4:Article17 [PMID: 16646834]
  27. Nucleic Acids Res. 2020 Jan 8;48(D1):D845-D855 [PMID: 31680165]
  28. Nature. 2013 Jun 13;498(7453):236-40 [PMID: 23685454]
  29. Development. 2015 Jun 15;142(12):2094-108 [PMID: 26081571]
  30. Semin Reprod Med. 2018 May;36(3-04):177-182 [PMID: 30866004]
  31. Cell Res. 2020 Dec;30(12):1109-1126 [PMID: 32690901]
  32. Sci Rep. 2017 Apr 20;7:46705 [PMID: 28425454]
  33. Neonatology. 2018;113(4):393-399 [PMID: 29852488]
  34. Cell Res. 2018 Jul;28(7):730-745 [PMID: 29867213]
  35. Nat Biotechnol. 2015 May;33(5):495-502 [PMID: 25867923]

Word Cloud

Similar Articles

Cited By