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The Journal of experimental medicine
09 05, 2022;219 (9):

Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish.

Sara A Rubin, Chloé S Baron, Cecilia Pessoa Rodrigues, Madeleine Duran, Alexandra F Corbin, Song P Yang, Cole Trapnell, Leonard I Zon
Author Information
  1. Sara A Rubin: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  2. Chloé S Baron: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  3. Cecilia Pessoa Rodrigues: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  4. Madeleine Duran: Department of Genome Sciences, University of Washington, Seattle, WA. ORCID
  5. Alexandra F Corbin: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  6. Song P Yang: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
  7. Cole Trapnell: Department of Genome Sciences, University of Washington, Seattle, WA. ORCID
  8. Leonard I Zon: Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA. ORCID
PMID: 35938989 DOI: 10.1084/jem.20220038

Abstract

The zebrafish has proven to be a valuable model organism for studying hematopoiesis, but relatively little is known about zebrafish immune cell development and functional diversity. Elucidating key aspects of zebrafish lymphocyte development and exploring the breadth of effector functions would provide valuable insight into the evolution of adaptive immunity. We performed single-cell RNA sequencing on ∼70,000 cells from the zebrafish marrow and thymus to establish a gene expression map of zebrafish immune cell development. We uncovered rich cellular diversity in the juvenile and adult zebrafish thymus, elucidated B- and T-cell developmental trajectories, and transcriptionally characterized subsets of hematopoietic stem and progenitor cells and early thymic progenitors. Our analysis permitted the identification of two dendritic-like cell populations and provided evidence in support of the existence of a pre-B cell state. Our results provide critical insights into the landscape of zebrafish immunology and offer a foundation for cellular and genetic studies.

References

J Immunol. 1994 Jun 15;152(12):5653-9 [PMID: 8207198]
FEBS Lett. 2002 Sep 11;527(1-3):205-10 [PMID: 12220661]
Cell Rep. 2016 Feb 2;14(4):966-977 [PMID: 26804912]
J Immunol. 2006 Aug 15;177(4):2463-76 [PMID: 16888008]
Blood. 2010 Nov 11;116(19):3944-54 [PMID: 20713961]
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18467-72 [PMID: 16339308]
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17129-33 [PMID: 19805112]
Int J Mol Sci. 2019 Aug 26;20(17): [PMID: 31454991]
J Leukoc Biol. 2020 Mar;107(3):431-443 [PMID: 31909502]
Nature. 2018 Feb 22;554(7693):475-480 [PMID: 29443965]
Blood Adv. 2022 Mar 8;6(5):1474-1488 [PMID: 34979548]
Bioinformatics. 2010 Feb 1;26(3):363-9 [PMID: 20007255]
Science. 2003 Nov 7;302(5647):1041-3 [PMID: 14605368]
Cell. 1989 Dec 22;59(6):1035-48 [PMID: 2598259]
Dev Biol. 2012 Jun 15;366(2):185-94 [PMID: 22537494]
Dev Biol. 2002 Jun 15;246(2):274-95 [PMID: 12051816]
J Leukoc Biol. 2020 Jun;107(6):1045-1055 [PMID: 31994778]
Nat Methods. 2018 May;15(5):379-386 [PMID: 29630061]
Development. 2015 Mar 15;142(6):1050-61 [PMID: 25758220]
J Histochem Cytochem. 2004 Feb;52(2):243-52 [PMID: 14729876]
PLoS Genet. 2020 Oct 26;16(10):e1008800 [PMID: 33104690]
Cytokine Growth Factor Rev. 2006 Oct;17(5):349-66 [PMID: 16911870]
Science. 2016 Jul 29;353(6298):aaf7907 [PMID: 27229144]
Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3333-8 [PMID: 18303114]
Immunity. 2019 Jan 15;50(1):77-90.e5 [PMID: 30611612]
Organogenesis. 2016 Apr 2;12(2):78-93 [PMID: 27078170]
Biochem Biophys Res Commun. 2008 Mar 14;367(3):693-9 [PMID: 18166152]
Genes Dev. 2022 Apr 1;36(7-8):391-407 [PMID: 35487686]
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20572-7 [PMID: 23188800]
Dev Biol. 1997 Feb 15;182(2):331-41 [PMID: 9070331]
J Immunol. 2011 Jun 15;186(12):7060-6 [PMID: 21562163]
Elife. 2016 Jan 27;5:e11813 [PMID: 26814702]
Stem Cells. 2014 Jun;32(6):1380-9 [PMID: 24497003]
Immunogenetics. 2012 Jan;64(1):49-58 [PMID: 21748441]
J Exp Med. 2004 Aug 16;200(4):493-505 [PMID: 15302902]
Gene. 2007 Oct 15;401(1-2):154-64 [PMID: 17719728]
Fibrogenesis Tissue Repair. 2013 May 10;6(1):10 [PMID: 23663505]
Hum Mol Genet. 2008 Oct 15;17(20):3204-11 [PMID: 18653748]
J Biol Chem. 2002 May 24;277(21):19131-8 [PMID: 11891219]
Front Immunol. 2021 Sep 30;12:740047 [PMID: 34659232]
Nat Rev Immunol. 2008 Jan;8(1):9-21 [PMID: 18097446]
Blood Adv. 2021 Jul 13;5(13):2687-2700 [PMID: 34170285]
Front Immunol. 2017 Jan 09;7:675 [PMID: 28119690]
Blood. 2010 Jun 3;115(22):4605-13 [PMID: 20086246]
Haematologica. 2017 Mar;102(3):e93-e96 [PMID: 27909223]
FEBS Lett. 2011 Oct 20;585(20):3337-41 [PMID: 21959040]
Immunity. 2012 Feb 24;36(2):298-309 [PMID: 22342843]
Blood. 2003 Aug 15;102(4):1298-306 [PMID: 12714519]
PLoS One. 2014 Jun 24;9(6):e99956 [PMID: 24959908]
Open Biol. 2021 Aug;11(8):210120 [PMID: 34375547]
Cell Rep. 2022 Mar 1;38(9):110446 [PMID: 35235777]
Immunogenetics. 2010 Jan;62(1):23-9 [PMID: 20054533]
Hum Immunol. 2002 Dec;63(12):1111-9 [PMID: 12480254]
Fish Shellfish Immunol. 2011 Nov;31(5):697-703 [PMID: 20933599]
Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118-22 [PMID: 6287467]
Gene. 2001 Dec 27;281(1-2):43-51 [PMID: 11750126]
Nat Methods. 2017 Oct;14(10):979-982 [PMID: 28825705]
Genome Biol. 2019 Dec 23;20(1):296 [PMID: 31870423]
Bioinformatics. 2021 Dec 7;37(23):4578-4580 [PMID: 34244710]
Nat Immunol. 2006 Mar;7(3):274-83 [PMID: 16474395]
Cold Spring Harb Perspect Biol. 2014 Jun 02;6(6): [PMID: 24890514]
Front Neuroendocrinol. 1999 Jul;20(3):157-98 [PMID: 10433861]
Blood Sci. 2020 Dec 1;3(1):14-19 [PMID: 35399207]
Open Biol. 2017 Aug;7(8): [PMID: 28835569]
Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21040-5 [PMID: 23213226]
Nat Immunol. 2009 Aug;10(8):848-56 [PMID: 19597499]
PLoS One. 2016 Sep 21;11(9):e0162358 [PMID: 27654936]
Mol Biol Cell. 2010 Feb 15;21(4):562-71 [PMID: 20016009]
Elife. 2020 Aug 25;9: [PMID: 32840480]
Stem Cells Int. 2015;2015:362753 [PMID: 26257789]
J Exp Med. 2003 Jul 21;198(2):305-13 [PMID: 12874263]
Proc Natl Acad Sci U S A. 2004 May 11;101(19):7369-74 [PMID: 15123839]
Nat Immunol. 2004 May;5(5):539-45 [PMID: 15077109]
Front Immunol. 2022 Jan 27;13:820152 [PMID: 35154138]
Blood. 2013 Aug 22;122(8):e1-11 [PMID: 23861249]
Elife. 2020 May 05;9: [PMID: 32367800]
Cell Rep. 2016 Nov 1;17(6):1518-1531 [PMID: 27806292]
Gigascience. 2020 Dec 26;9(12): [PMID: 33367645]
Nat Methods. 2014 Jun;11(6):637-40 [PMID: 24747814]
Elife. 2017 Mar 27;6: [PMID: 28346141]
EMBO J. 1991 Nov;10(11):3409-17 [PMID: 1915300]
Front Immunol. 2021 May 04;12:677707 [PMID: 34017346]
Sci Immunol. 2018 Jul 6;3(25): [PMID: 29980619]
PLoS One. 2015 Oct 07;10(10):e0138949 [PMID: 26445458]
Blood. 2008 Nov 15;112(10):4028-38 [PMID: 18799728]
Sci Rep. 2019 Mar 18;9(1):4768 [PMID: 30886241]
Genome Res. 2017 Mar;27(3):451-461 [PMID: 28087841]
J Neurochem. 2013 May;125(3):399-409 [PMID: 23418755]
Mol Cancer. 2019 Dec 9;18(1):180 [PMID: 31815635]
J Immunol. 2016 Nov 1;197(9):3520-3530 [PMID: 27694495]
Chronobiol Int. 2010 Sep;27(8):1509-31 [PMID: 20854132]
Leukemia. 2010 Jul;24(7):1249-57 [PMID: 20520638]
Cell Mol Life Sci. 2004 Oct;61(19-20):2614-23 [PMID: 15526166]
PLoS One. 2022 Mar 23;17(3):e0264776 [PMID: 35320267]
Science. 2008 Nov 14;322(5904):1097-100 [PMID: 19008445]
Am J Pathol. 2007 Aug;171(2):386-95 [PMID: 17600130]
Blood. 2010 Jul 22;116(3):e1-11 [PMID: 20424185]
Immunity. 2016 Sep 20;45(3):626-640 [PMID: 27637148]
Cancers (Basel). 2022 Feb 17;14(4): [PMID: 35205759]
J Leukoc Biol. 2013 Feb;93(2):185-98 [PMID: 23066164]
Immunogenetics. 2016 May;68(5):365-79 [PMID: 26809968]
Front Immunol. 2021 Dec 02;12:747324 [PMID: 34925323]
Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9573-8 [PMID: 24979759]
Immunity. 2019 Nov 19;51(5):930-948.e6 [PMID: 31604687]
PLoS One. 2015 Jan 23;10(1):e0117513 [PMID: 25615614]
Mol Immunol. 2007 Mar;44(9):2324-31 [PMID: 17194477]
Dev Biol. 2011 Sep 15;357(2):518-31 [PMID: 21723274]
Cell Mol Life Sci. 2013 Dec;70(23):4537-53 [PMID: 23793512]
Haematologica. 2020 Jan 09;106(1):130-141 [PMID: 31919081]
Front Cell Dev Biol. 2020 Jul 24;8:564 [PMID: 32850777]
J Biol Chem. 2003 Oct 31;278(44):43460-9 [PMID: 12920129]
Nat Rev Immunol. 2009 Feb;9(2):125-35 [PMID: 19151747]
Nature. 2000 Nov 2;408(6808):57-63 [PMID: 11081504]
Blood. 2014 Apr 17;123(16):2518-29 [PMID: 24591202]
J Leukoc Biol. 2012 Dec;92(6):1177-86 [PMID: 22966131]
Blood. 2008 Feb 1;111(3):1147-56 [PMID: 17934068]
Mol Cell Endocrinol. 2010 May 14;320(1-2):145-52 [PMID: 20138960]
Nat Commun. 2018 Aug 1;9(1):3016 [PMID: 30069061]
Genome Res. 2015 Dec;25(12):1860-72 [PMID: 26430063]
Cancer Res. 2017 Jan 1;77(1):187-197 [PMID: 27821484]
Nat Immunol. 2005 Mar;6(3):295-302 [PMID: 15685175]
Immunity. 2004 Jun;20(6):735-45 [PMID: 15189738]
Mol Endocrinol. 1994 Jul;8(7):852-9 [PMID: 7984147]
Immunol Rev. 2010 May;235(1):93-104 [PMID: 20536557]
J Exp Med. 2017 Oct 2;214(10):2875-2887 [PMID: 28878000]
Dev Dyn. 2003 Nov;228(3):323-36 [PMID: 14579373]
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15850-5 [PMID: 20733076]
FEBS J. 2010 Jan;277(1):128-47 [PMID: 19961539]
Mol Pharmacol. 2019 Dec;96(6):809-818 [PMID: 31040166]
Sci Rep. 2020 Jul 16;10(1):11801 [PMID: 32678226]
Sci Immunol. 2022 Nov 18;7(77):eade0182 [PMID: 36367948]
Sci Rep. 2021 Apr 28;11(1):9164 [PMID: 33911146]
Front Immunol. 2012 Jul 18;3:214 [PMID: 22826713]
Immunity. 2011 Aug 26;35(2):299-311 [PMID: 21867929]
Nature. 1994 Sep 15;371(6494):221-6 [PMID: 8078582]
Sci Immunol. 2018 Nov 16;3(29): [PMID: 30446505]
Leukemia. 2018 Aug;32(8):1860-1865 [PMID: 29749398]
Immunogenetics. 2007 Sep;59(9):735-44 [PMID: 17701034]
J Immunol. 2012 Jun 1;188(11):5571-84 [PMID: 22547699]
Nature. 1995 Jun 1;375(6530):418-21 [PMID: 7760937]
Cell. 2011 Apr 29;145(3):383-397 [PMID: 21529712]
PLoS Negl Trop Dis. 2014 Sep 25;8(9):e3194 [PMID: 25255101]
J Immunol. 2017 Sep 1;199(5):1706-1715 [PMID: 28739882]
Nat Biotechnol. 2014 Apr;32(4):381-386 [PMID: 24658644]
Immunity. 2007 Jun;26(6):715-25 [PMID: 17582344]
Blood. 1997 Jan 15;89(2):688-700 [PMID: 9002973]
Immunity. 2004 Apr;20(4):367-79 [PMID: 15084267]
Nat Protoc. 2018 Nov;13(11):2685-2713 [PMID: 30353175]
Cancer Cell Int. 2015 Nov 05;15:106 [PMID: 26549987]
Microbes Infect. 2002 Nov;4(14):1469-78 [PMID: 12475637]
Dev Dyn. 2002 Sep;225(1):87-94 [PMID: 12203724]
Trends Immunol. 2018 Feb;39(2):86-98 [PMID: 29162323]
Cell. 2019 Jun 13;177(7):1888-1902.e21 [PMID: 31178118]
Science. 1990 Jun 22;248(4962):1517-23 [PMID: 2360047]
Development. 2008 May;135(10):1853-62 [PMID: 18417622]
Genome Biol. 2019 Mar 19;20(1):59 [PMID: 30890159]
Blood. 2014 Jul 3;124(1):24-32 [PMID: 24829207]
Nature. 2019 Feb;566(7745):496-502 [PMID: 30787437]
Nat Commun. 2021 Feb 17;12(1):1096 [PMID: 33597545]
Thromb Haemost. 1994 Jul;72(1):1-15 [PMID: 7974356]
Immunogenetics. 1997;45(6):394-404 [PMID: 9089097]
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13814-9 [PMID: 19666492]
Blood Adv. 2021 Jul 13;5(13):2673-2686 [PMID: 34170284]
J Biol Chem. 2002 Apr 26;277(17):14954-64 [PMID: 11836249]
Immunogenetics. 2008 Jul;60(7):383-97 [PMID: 18560827]
Zebrafish. 2021 Dec;18(6):343-345 [PMID: 34935497]
Nat Immunol. 2013 Jun;14(6):633-43 [PMID: 23624555]
Immunol Rev. 2014 Sep;261(1):102-15 [PMID: 25123279]
J Am Soc Nephrol. 2018 Jan;29(1):138-154 [PMID: 29217759]
PLoS One. 2015 Jun 17;10(6):e0126378 [PMID: 26083432]
Nat Immunol. 2007 Dec;8(12):1337-44 [PMID: 17965716]
Nat Commun. 2017 Dec 11;8(1):2045 [PMID: 29229905]
Science. 2007 Jan 12;315(5809):230-3 [PMID: 17218525]
Mol Immunol. 1996 Apr;33(6):511-20 [PMID: 8700167]
Nat Commun. 2019 Apr 3;10(1):1523 [PMID: 30944313]
Immunity. 2006 Dec;25(6):963-75 [PMID: 17157041]
Front Aging Neurosci. 2019 Aug 07;11:204 [PMID: 31447664]
Nature. 2002 Jan 31;415(6871):536-41 [PMID: 11823861]
Nat Rev Immunol. 2020 Apr;20(4):239-253 [PMID: 31804611]
J Immunol. 2003 Nov 15;171(10):5091-9 [PMID: 14607907]
Nat Protoc. 2018 Apr;13(4):599-604 [PMID: 29494575]
Clin Cancer Res. 2005 Sep 15;11(18):6442-9 [PMID: 16166418]
Biology (Basel). 2020 Dec 25;10(1): [PMID: 33375568]
Genes Dev. 2001 Nov 1;15(21):2877-85 [PMID: 11691838]
J Exp Med. 2016 May 30;213(6):979-92 [PMID: 27139488]
Immunity. 2012 Jan 27;36(1):55-67 [PMID: 22261438]
Front Immunol. 2017 Jan 20;8:32 [PMID: 28163708]
Cancer Cell. 2013 Nov 11;24(5):575-88 [PMID: 24183681]
Cell Stem Cell. 2014 Sep 4;15(3):350-364 [PMID: 25130491]
Nat Commun. 2017 Jan 16;8:14049 [PMID: 28091601]
BMC Genomics. 2005 Nov 08;6:156 [PMID: 16277664]
Immunogenetics. 2000 Sep;51(11):915-23 [PMID: 11003385]
Nat Methods. 2020 Jan;17(1):45-49 [PMID: 31740822]
Cell Stem Cell. 2016 Aug 4;19(2):266-277 [PMID: 27345837]
Cell. 2009 Jul 10;138(1):186-97 [PMID: 19559469]
Front Immunol. 2021 Sep 09;12:712572 [PMID: 34566967]
Front Immunol. 2019 Dec 02;10:2720 [PMID: 31832066]
Science. 1993 Aug 27;261(5125):1171-5 [PMID: 8356451]
Nat Biotechnol. 2018 Jun;36(5):442-450 [PMID: 29608178]
Cell. 2019 Oct 3;179(2):527-542.e19 [PMID: 31585086]
Blood. 1996 Aug 15;88(4):1234-47 [PMID: 8695841]

Grants

  1. F30 HL152628/NHLBI NIH HHS
  2. P01 HL131477/NHLBI NIH HHS
  3. R01 HL144780/NHLBI NIH HHS
  4. T32 HL007574/NHLBI NIH HHS

MeSH Term

Animals
Hematopoiesis
Hematopoietic Stem Cells
Precursor Cells, B-Lymphoid
Single-Cell Analysis
Thymus Gland
Zebrafish
Journal Article Research Support, N.I.H., Extramural

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