RESEARCH ARTICLE

Neoblast-enriched zinc finger protein FIR1 triggers local proliferation during planarian regeneration

  • Xiao-Shuai Han 1 ,
  • Chen Wang 1 ,
  • Fang-hao Guo 1 ,
  • Shuang Huang 2 ,
  • Yong-Wen Qin 2 ,
  • Xian-Xian Zhao 2 ,
  • Qing Jing , 1,2
Expand
  • 1. Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China
  • 2. Department of Cardiology, Changhai Hospital, Shanghai 200433, China

Received date: 06 Jul 2017

Accepted date: 09 Jan 2018

Published date: 31 Jan 2019

Copyright

2018 The Author(s) 2018

Abstract

Regeneration, relying mainly on resident adult stem cells, is widespread. However, the mechanism by which stem cells initiate proliferation during this process in vivo is unclear. Using planarian as a model, we screened 46 transcripts showing potential function in the regulation of local stem cell proliferation following 48 h regeneration. By analyzing the regeneration defects and the mitotic activity of animals under administration of RNA interference (RNAi), we identified factor for initiating regeneration 1 (Fir1) required for local proliferation. Our findings reveal that Fir1, enriched in neoblasts, promotes planarian regeneration in any tissue-missing context. Further, we demonstrate that DIS3 like 3′-5′ exoribonuclease 2 (Dis3l2) is required for Fir1 phenotype. Besides, RNAi knockdown of Fir1 causes a decrease of neoblast wound response genes following amputation. These findings suggest that Fir1 recognizes regenerative signals and promotes DIS3L2 proteins to trigger neoblast proliferation following amputation and provide a mechanism critical for stem cell response to injury.

Cite this article

Xiao-Shuai Han , Chen Wang , Fang-hao Guo , Shuang Huang , Yong-Wen Qin , Xian-Xian Zhao , Qing Jing . Neoblast-enriched zinc finger protein FIR1 triggers local proliferation during planarian regeneration[J]. Protein & Cell, 2019 , 10(1) : 43 -59 . DOI: 10.1007/s13238-018-0512-0

1
Almuedo-Castillo M, Crespo X, Seebeck F, Bartscherer K, Salò E, Adell T, Aboobaker AA (2014) JNK Controls the onset of mitosis in planarian stem cells and triggers apoptotic cell death required for regeneration and remodeling. PLoS Genetics 10(6):e1004400

DOI

2
Astuti D, Morris MR, Cooper WN, Staals RH, Wake NC, Fews GA, Gill H, Gentle D, Shuib S, Ricketts CJ (2012) Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet 44:277–284

DOI

3
Bardeen C, Baetjer F (1904) The inhibitive action of the Roentgen rays onregeneration in planarians. J Exp Zool 1:191–195

DOI

4
Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432:324–331

DOI

5
Best JB, Hand S, Rosenvold R (1968) Mitosis in normal and regenerating planarians. J Exp Zool 168(2):157–167

DOI

6
Blassberg RA, Felix DA, Tejada-Romero B, Aboobaker AA (2013) PBX/extradenticle is required to re-establish axial structures and polarity during planarian regeneration. Development 140(4):730–739

DOI

7
Bonuccelli L, Rossi L, Lena A, Scarcelli V, Rainaldi G, Evangelista M, Iacopetti P, Gremigni V, Salvetti A (2010) An RbAp48-like gene regulates adult stem cells in planarians. J Cell Sci 123(5):690–698

DOI

8
Böser A, Drexler HC, Reuter H, Schmitz H, Wu G, Schöler HR, Gentile L, Bartscherer K (2013) SILAC proteomics of planarians identifies Ncoa5 as a conserved component of pluripotent stem cells. Cell Rep 5(4):1142–1155

DOI

9
Carlson ME, Hsu M, Conboy IM (2008) Imbalance between pSmad3 andNotch induces CDK inhibitors in old muscle stem cells. Nature 454:528–532

DOI

10
Chang HM, Triboulet R, Thornton JE, Gregory RI (2013) A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature 497:244–248

DOI

11
Chen CCG, Wang IE, Reddien PW (2013) pbx is required for pole and eye regeneration in planarians. Development 140(4):719–729

DOI

12
Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlstrom H, Lendahl U, Frisen J (2000) Generalized potential of adult neural stem cells. Science 288:1660–1663

DOI

13
Cowles MW, Hubert A, Zayas RM (2012) A Lissencephaly-1 homologue is essential for mitotic progression in the planarian Schmidtea mediterranea. Dev Dyn 241:901–910

DOI

14
Dubois F (1949) Contribution á l ’ètude de la migration des cellules de règènèration chez les Planaires dulcicoles. Bull Biol Fr Belg 83:213–283

15
Fuchs E, Segre JA (2000) Stem cells: a new lease on life. Cell 100:143–155

DOI

16
Fuchs Y, Steller H (2015) Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nature Reviews Molecular Cell Biology 16(6):329–344

DOI

17
Gavino MA, Wenemoser D, Wang IE, Reddien PW (2013) Tissue absence initiates regeneration through follistatin-mediated inhibition of activin signaling. Elife 2:e00247

DOI

18
Gentile L, Cebria F, Bartscherer K (2011) The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration. Dis Models Mech 4:12–19

DOI

19
Gonzalez-Estevez C, Felix DA, Smith MD, Paps J, Morley SJ, James V, Sharp TV, Aboobaker AA (2012) SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth in planarians. Plos Genetics 8:e1002619

DOI

20
Govindasamy N, Murthy S, Ghanekar Y (2014) Slow-cycling stem cells in hydra contribute to head regeneration. Biol Open 3:1236–1244

DOI

21
Guo T, Peters AH, Newmark PA (2006) A bruno-like gene is required for stem cell maintenance in planarians. Dev Cell 11(2):159–169

DOI

22
Hayashi T, Asami M, Higuchi S, Shibata N, Agata K (2006) Isolation of planarian X-ray-sensitive stem cells by fluorescence-activated cell sorting. Dev Growth Differ 48:371–380

DOI

23
Hollenbach JP, Resch AM, Palakodeti D, Graveley BR, Heinen CD, Martin G (2011) Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells. PLoS ONE 6(7):e21808

DOI

24
Hopman AH, Ramaekers FC, Speel EJ (1998) Rapid synthesis of biotin-, digoxigenin-, trinitrophenyl-, and fluorochrome-labeled tyramides and their application for In situ hybridization using CARD amplification. J Histochem Cytochem 46:771–777

DOI

25
Kao D, Felix D, Aboobaker A (2013) The planarian regeneration transcriptome reveals a shared but temporally shifted regulatory program between opposing head and tail scenarios. BMC Genomics 14:797

DOI

26
King RS, Newmark PA (2013) In situ hybridization protocol for enhanced detection of gene expression in the planarian Schmidtea mediterranea. BMC Dev Biol 13:8

DOI

27
Labbe RM, Irimia M, Currie KW, Lin A, Zhu SJ, Brown DD, Ross EJ, Voisin V, Bader GD, Blencowe BJ (2012) A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals. Stem Cells 30:1734–1745

DOI

28
Lapan SW, Reddien PW (2011) dlx and sp6-9 Control optic cup regeneration in a prototypic eye. PLoS Genet 7:e1002226

DOI

29
Li YQ, Zeng A, Han XS, Wang C, Li G, Zhang ZC, Wang JY, Qin YW, Jing Q (2011) Argonaute-2 regulates the proliferation of adult stem cells in planarian. Cell Res 21:1750–1754

DOI

30
Morgan T (1898) Experimental studies of the regeneration of Planaria maculata. Arch Entw Mech Org 7:364–397

DOI

31
Morgan TH (1901) Regeneration. Macmillan, New York, p 316

DOI

32
Newmark PA, Sanchez AAlvarado (2000) Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol 220:142–153

DOI

33
Onal P, Grun D, Adamidi C, Rybak A, Solana J, Mastrobuoni G, Wang Y, Rahn HP, Chen W, Kempa S (2012) Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells. EMBO J 31:2755–2769

DOI

34
Oviedo NJ, Levin M (2007) smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis. Development 134(17):3121–3131

DOI

35
Palakodeti D, Smielewska M, Lu YC, Yeo GW, Graveley BR (2008) The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians. RNA 14 (6):1174–1186

DOI

36
Passamaneck YJ, Martindale MQ (2012) Cell proliferation is necessary for the regeneration of oral structures in the anthozoan cnidarian Nematostella vectensis. BMC Dev Biol 12:34

DOI

37
Pearson BJ, Sanchez Alvarado A(2010) A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages. Development 137:213–221

DOI

38
Pearson BJ, Eisenhoffer GT, Gurley KA, Rink JC, Miller DE, Sanchez Alvarado A (2009) Formaldehyde-based whole-mount in situ hybridization method for planarians. Dev Dyn 238:443–450

DOI

39
Pellettieri J, Sanchez Alvarado A (2007) Cell turnover and adult tissue homeostasis: from humans to planarians. Annu Rev Genet 41:83–105

DOI

40
Pellettieri J, Fitzgerald P, Watanabe S, Mancuso J, Green DR, Sanchez Alvarado A (2010) Cell death and tissue remodeling in planarian regeneration. Dev Biol 338:76–85

DOI

41
Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080

DOI

42
Reddien PW, Sanchez AAlvarado (2004) Fundamentals of planarian regeneration. Annu Rev Cell Dev Biol 20:725–757

DOI

43
Reddien PW, Oviedo NJ, Jennings JR, Jenkin JC, Alvarado AS (2005a) SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310:1327–1330

DOI

44
Reddien PW, Oviedo NJ, Jennings JR, Jenkin JC, Sanchez Alvarado A (2005b) SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310:1327–1330

DOI

45
Rossi L, Salvetti A, Marincola FM, Lena A, Deri P, Mannini L, Batistoni R, Wang E, Gremigni V (2007) Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile. Genome Biol 8:R62

DOI

46
Rouhana L, Shibata N, Nishimura O, Agata K (2010) Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance. Dev Biol 341(2):429–443

DOI

47
Rouhana L, Vieira AP, Roberts-Galbraith RH, Newmark PA (2012) PRMT5 and the role of symmetrical dimethylarginine in chromatoid bodies of planarian stem cells. Development 139:1083–1094

DOI

48
Rouhana L, Weiss JA, Forsthoefel DJ, Lee H, King RS, Inoue T, Shibata N, Agata K, Newmark PA (2013) RNA interference by feeding in vitro-synthesized double-stranded RNA to planarians: methodology and dynamics. Dev Dyn 242:718–730

DOI

49
Salvetti A (2005) DjPum, a homologue of Drosophila Pumilio, is essential to planarian stem cell maintenance. Development 132 (8):1863–1874

DOI

50
Sanchez Alvarado A (2000) Regeneration in the metazoans: why does it happen? BioEssays 22:578–590

DOI

51
Sanchez Alvarado A (2003) The freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration. Curr Opin Genet Dev 13:438–444

DOI

52
Sanchez Alvarado A, Newmark PA, Robb SM, Juste R (2002) The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration. Development 129:5659–5665

DOI

53
Scimone ML, Meisel J, Reddien PW (2010) The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea. Development 137:1231–1241

DOI

54
Scimone ML, Kravarik KM, Lapan SW, Reddien PW (2014) Neoblast specialization in regeneration of the planarian Schmidtea mediterranea. Stem Cell Rep 3:339–352

DOI

55
Seifert AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M (2012) Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature 489:561–565

DOI

56
Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N (2010) The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137:4147–4158

DOI

57
Solana J, Kao D, Mihaylova Y, Jaber-Hijazi F, Malla S, Wilson R, Aboobaker A (2012) Defining the molecular profile of planarian pluripotent stem cells using a combinatorial RNAseq, RNA interference and irradiation approach. Genome Biol 13:R19

DOI

58
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

DOI

59
Ustianenko D, Hrossova D, Potesil D, Chalupnikova K, Hrazdilova K, Pachernik J, Cetkovska K, Uldrijan S, Zdrahal Z, Vanacova S (2013) Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs. RNA 19:1632–1638

DOI

60
van Wolfswinkel JC, Wagner DE, Reddien PW (2014) Single-cell analysis reveals functionally distinct classes within the planarian stem cell compartment. Cell Stem Cell 15:326–339

DOI

61
Wagner DE, Wang IE, Reddien PW (2011) Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332:811–816

DOI

62
Wagner DE, Ho JJ, Reddien PW (2012) Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell 10:299–311

DOI

63
Wang YZ, Yamagami T, Gan Q, Wang Y, Zhao T, Hamad S, Lott P, Schnittke N, Schwob JE, Zhou CJ (2011) Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration. J Cell Sci 124:1553–1563

DOI

64
Wang C, Han XS, Li FF, Huang S, Qin YW, Zhao XX, Jing Q (2016) Forkhead containing transcription factor Albino controls tetrapyrrole-based body pigmentation in planarian. C ell Discov. https://doi.org/10.1038/celldisc.2016.29

DOI

65
Wenemoser D, Reddien PW (2010) Planarian regeneration involves distinct stem cell responses to wounds and tissue absence. Dev Biol 344:979–991

DOI

66
Wenemoser D, Lapan SW, Wilkinson AW, Bell GW, Reddien PW (2012) A molecular wound response program associated with regeneration initiation in planarians. Genes Dev 26:988–1002

DOI

67
Wurtzel O, Cote LE, Poirier A, Satija R, Regev A, Reddien PW (2015) A Generic and Cell-Type-Specific Wound Response Precedes Regeneration in Planarians. Dev Cell 35:632–645

DOI

68
Zayas RM, Hernández A, Habermann B, Wang Y, Stary JM, Newmark PA (2005) The planarian Schmidtea mediterranea as a model for epigenetic germ cell specification: Analysis of ESTs from the hermaphroditic strain. Proc Nat Acad Sci 102 (51):18491–18496

DOI

69
Zeng A, Li YQ, Wang C, Han XS, Li G, Wang JY, Li DS, Qin YW, Shi Y, Brewer G(2013) Heterochromatin protein 1 promotes selfrenewal and triggers regenerative proliferation in adult stem cells. J Cell Biol 201:409–425

DOI

70
Zhu SJ, Pearson BJ (2013) The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians. Dev Biol 373 (2):442–452

DOI

71
Zhu SJ, Hallows SE, Currie KW, Xu C, Pearson BJ (2015) A mex3 homolog is required for differentiation during planarian stem cell lineage development. eLife 4

DOI

Outlines

/