Skip to content
naulon

No retraction, correction or concern found when last checked on Nov 2, 2026.

Plant stem cell maintenance involves direct transcriptional repression of differentiation program

Ram Kishor Yadav, Mariano Perales, Jérémy Gruel and 5 more

Molecular Systems Biology · 2013 · CC BY-NC-SA

doi:10.1038/msb.2013.8

Abstract

In animal systems, master regulatory transcription factors (TFs) mediate stem cell maintenance through a direct transcriptional repression of differentiation promoting TFs. Whether similar mechanisms operate in plants is not known. In plants, shoot apical meristems serve as reservoirs of stem cells that provide cells for all above ground organs. WUSCHEL, a homeodomain TF produced in cells of the niche, migrates into adjacent cells where it specifies stem cells. Through high-resolution genomic analysis, we show that WUSCHEL represses a large number of genes that are expressed in differentiating cells including a group of differentiation promoting TFs involved in leaf development. We show that WUS directly binds to the regulatory regions of differentiation promoting TFs; KANADI1, KANADI2, ASYMMETRICLEAVES2 and YABBY3 to repress their expression. Predictions from a computational model, supported by live imaging, reveal that WUS-mediated repression prevents premature differentiation of stem cell progenitors, being part of a minimal regulatory network for meristem maintenance. Our work shows that direct transcriptional repression of differentiation promoting TFs is an evolutionarily conserved logic for stem cell regulation.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 53

  1. 1.

    Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006 ) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315–326

    Not in our library10.1016/j.cell.2006.02.041

  2. 2.

    Bhatt AM, Etchells JP, Canales C, Lagodienko A, Dickinson H (2004 ) VAAMANA-a BEL1-like homeodomain protein, interacts with KNOX proteins BP and STM and regulates inflorescence stem growth in Arabidopsis. Gene 328: 103–111

    Not in our library10.1016/j.gene.2003.12.033

  3. 3.

    Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005 ) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122: 947–956

    Not in our library10.1016/j.cell.2005.08.020

  4. 4.

    Brand U, Grunewald M, Hobe M, Simon R (2002 ) Regulation of CLV3 expression by two homeobox genes in Arabidopsis. Plant Physiol 129: 565–575

    Not in our library10.1104/pp.001867

  5. 5.

    Brand U, Fletcher JC, Hobe M, Meyerowitz EM, Simon R (2000 ) Dependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3 activity. Science 289: 617–619

    Not in our library10.1126/science.289.5479.617

  6. 6.

    Busch W, Miotk A, Ariel FD, Zhao Z, Forner J, Daum G, Suzaki T, Schuster C, Schultheiss SJ, Leibfried A, Haubeiss S, Ha N, Chan RL, Lohmann JU (2010 ) Transcriptional control of a plant stem cell niche. Dev Cell 18: 849–861

    Not in our library10.1016/j.devcel.2010.03.012

  7. 7.

    Chickarmane VS, Gordon SP, Tarr PT, Heisler MG, Meyerowitz EM (2012 ) Cytokinin signaling as a positional cue for patterning the apical-basal axis of the growing Arabidopsis shoot meristem. Proc Natl Acad Sci USA 109: 4002–4007

    Not in our library10.1073/pnas.1200636109

  8. 8.

    Clark SE, Williams RW, Meyerowitz EM (1997 ) The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and floral meristem size in Arabidopsis. Cell 89: 575–585

    Not in our library10.1016/s0092-8674(00)80239-1

  9. 9.

    Dhondt S, Coppens F, De Winter F, Swarup K, Merks RM, Inzé D, Bennett MJ, Beemster GT (2010 ) SHORT-ROOT and SCARECROW regulate leaf growth in Arabidopsis by stimulating S-phase progression of the cell cycle. Plant Physiol 154: 1183–1195

    Not in our library10.1104/pp.110.158857

  10. 10.

    Ding Z, Friml J (2010 ) Auxin regulates distal stem cell differentiation in Arabidopsis roots. Proc Natl Acad Sci USA 107: 12046–12051

    Not in our library10.1073/pnas.1000672107

  11. 11.

    Douglas SJ, Chuck G, Dengler RE, Pelecanda L, Riggs CD (2002 ) KNAT1 and ERECTA regulate inflorescence architecture in Arabidopsis. Plant Cell 14: 547–558

    Not in our library10.1105/tpc.010391

  12. 12.

    Fletcher JC, Brand U, Running MP, Simon R, Meyerowitz EM (1999 ) Signaling of cell fate decisions by CLAVATA3 in Arabidopsis shoot meristems. Science 283: 1911–1914

    Not in our library10.1126/science.283.5409.1911

  13. 13.

    Gardiner J, Sherr I, Scarpella E (2010 ) Expression of DOF genes identifies early stages of vascular development in Arabidopsis leaves. Int J Dev Biol 54: 1389–1396

    Not in our library10.1387/ijdb.093006jg

  14. 14.

    Goldshmidt A, Alvarez JP, Bowman JL, Eshed Y (2008 ) Signals derived from YABBY gene activities in organ primordia regulate growth and partitioning of Arabidopsis shoot apical meristems. Plant Cell 20: 1217–1230

    Not in our library10.1105/tpc.107.057877

  15. 15.

    Gordon SP, Chickarmane VS, Ohno C, Meyerowitz EM (2009 ) Multiple feedback loops through cytokinin signaling control stem cell number within the Arabidopsis shoot meristem. Proc Natl Acad Sci USA 106: 16529–16534

    Not in our library10.1073/pnas.0908122106

  16. 16.

    Ikeda M, Mitsuda N, Ohme-Takagi M (2009 ) Arabidopsis WUSCHEL is a bifunctional transcription factor that acts as a repressor in stem cell regulation and as an activator in floral patterning. Plant Cell 21: 3493–3505

    Not in our library10.1105/tpc.109.069997

  17. 17.

    Jönsson H, Heisler M, Reddy GV, Agrawal V, Gor V, Shapiro BE, Mjolsness E, Meyerowitz EM (2005 ) Modeling the organization of the WUSCHEL expression domain in the shoot apical meristem. Bioinformatics 21(Suppl 1): i232

    Not in our library10.1093/bioinformatics/bti1036

  18. 18.

    Jönsson H, Shapiro BE, Meyerowitz EM, Mjolsness E (2003 ) Signalling in multicellular models of plant development. In On Growth, Form, and Computers Kumar S, Bentley P (eds) pp 156–161London: Academic Press,

    Not in our library

  19. 19.

    Kerstetter RA, Bollman K, Taylor RA, Bomblies K, Poethig RS (2001 ) KANADI regulates organ polarity in Arabidopsis. Nature 411: 706–708

    Not in our library10.1038/35079629

  20. 20.

    Kim JH, Choi D, Kende H (2003 ) The AtGRF family of putative transcription factors is involved in leaf and cotyledon growth in Arabidopsis. Plant J 36: 94–104

    Not in our library10.1046/j.1365-313x.2003.01862.x

  21. 21.

    Kumaran MK, Bowman JL, Sundaresan V (2002 ) YABBY polarity genes mediate the repression of KNOX homeobox genes in Arabidopsis. Plant Cell 14: 2761–2770

    Not in our library10.1105/tpc.004911

  22. 22.

    Laux T, Mayer KF, Berger J, Jurgens G (1996 ) The WUSCHEL gene is required for shoot and floral meristem integrity in Arabidopsis. Development 122: 87–96

    Not in our library10.1242/dev.122.1.87

  23. 23.

    Leibfried A, To JP, Busch W, Stehling S, Kehle A, Demar M, Kieber JJ, Lohmann JU (2005 ) WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators. Nature 438: 1172–1175

    Not in our library10.1038/nature04270

  24. 24.

    Lin WC, Shuai B, Springer PS (2003 ) The Arabidopsis LATERAL ORGAN BOUNDARIES-domain gene ASYMMETRIC LEAVES2 functions in the repression of KNOX gene expression and in adaxial-abaxial patterning. Plant Cell 15: 2241–2252

    Not in our library10.1105/tpc.014969

  25. 25.

    Lincoln C, Long J, Yamaguchi J, Serikawa K, Hake S (1994 ) A knotted1-like homeobox gene in Arabidopsis is expressed in the vegetative meristem and dramatically alters leaf morphology when overexpressed in transgenic plants. Plant Cell 6: 1859–1876

    Not in our library10.1105/tpc.6.12.1859

  26. 26.

    Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL (2006 ) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38: 431–440

    Not in our library10.1038/ng1760

  27. 27.

    Lohmann JU, Hong RL, Hobe M, Busch MA, Parcy F, Simon R, Weigel D (2001 ) A molecular link between stem cell regulation and floral patterning in Arabidopsis. Cell 105: 793–803

    Not in our library10.1016/s0092-8674(01)00384-1

  28. 28.

    Mano Y, Nemoto K (2012 ) The pathway of auxin biosynthesis in plants. J Exp Bot 63: 2853–2872

    Not in our library10.1093/jxb/ers091

  29. 29.

    Mayer KF, Schoof H, Haecker A, Lenhard M, Jürgens G, Laux T (1998 ) Role of WUSCHEL in regulating stem cell fate in the Arabidopsis shoot meristem. Cell 95: 805–815

    Not in our library10.1016/s0092-8674(00)81703-1

  30. 30.

    Meyerowitz EM (1997 ) Genetic control of cell division patterns in developing plants. Cell 88: 299–308

    Not in our library10.1016/s0092-8674(00)81868-1

  31. 31.

    Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C (2007 ) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553–560

    Not in our library10.1038/nature06008

  32. 32.

    Muller R, Borghi L, Kwiatkowska D, Laufs P, Simon R (2006 ) Dynamic and compensatory responses of Arabidopsis shoot and floral meristems to CLV3 signaling. Plant Cell 18: 1188–1198

    Not in our library10.1105/tpc.105.040444

  33. 33.

    Ogawa M, Shinohara H, Sakagami Y, Matsubayashi Y (2008 ) Arabidopsis CLV3 peptide directly binds CLV1 ectodomain. Science 319: 294

    Not in our library10.1126/science.1150083

  34. 34.

    Ohashi-Ito K, Bergmann DC (2006 ) Arabidopsis FAMA controls the final proliferation/differentiation switch during stomatal development. Plant Cell 18: 2493–2505

    Not in our library10.1105/tpc.106.046136

  35. 35.

    Reddy GV (2008 ) Live-imaging stem cell homeostasis in the Arabidopsis shoot apex. Curr Opin Plant Biol 11: 88–93

    Not in our library10.1016/j.pbi.2007.10.012

  36. 36.

    Reddy GV, Meyerowitz EM (2005 ) Stem cell homeostasis and growth dynamics can be uncoupled in the Arabidopsis shoot apex. Science 310: 663–667

    Not in our library10.1126/science.1116261

  37. 37.

    Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B (2009 ) The role of DNA shape in protein-DNA recognition. Nature 461: 1248–1253

    Not in our library10.1038/nature08473

  38. 38.

    Rutjens B, Bao D, van Eck-Stouten E, Brand M, Smeekens S, Proveniers M (2009 ) Shoot apical meristem function in Arabidopsis requires the combined activities of three BEL1-like homeodomain proteins. Plant J 58: 641–654

    Not in our library10.1111/j.1365-313x.2009.03809.x

  39. 39.

    Sarkar KA, Luijten M, Miyashima S, Lenhard M, Hashimoto T, Nakajima K, Scheres B, Heidstra R, Laux T (2007 ) Conserved factors regulate signalling in Arabidopsis thaliana shoot and root stem cell organizers. Nature 446: 811–814

    Not in our library10.1038/nature05703

  40. 40.

    Schoof H, Lenhard M, Haecker A, Mayer KF, Jürgens G, Laux T (2000 ) The stem cell population of Arabidopsis shoot meristems in maintained by a regulatory loop between the CLAVATA and WUSCHEL genes. Cell 100: 635–644

    Not in our library10.1016/s0092-8674(00)80700-x

  41. 41.

    Slattery M, Riley T, Liu P, Abe N, Gomez-Alcala P, Dror I, Zhou T, Rohs R, Honig B, Bussemaker HJ, Mann RS (2011 ) Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell 147: 1270–1282

    Not in our library10.1016/j.cell.2011.10.053

  42. 42.

    Steeves TA, Sussex IM (1989 ) Patterns in Plant Development: Shoot Apical Meristem Mutants of Arabidopsis thaliana New York: Cambridge University Press,

    Not in our library

  43. 43.

    Takada S, Hibara K, Ishida T, Tasaka M (2001 ) The CUP-SHAPED COTYLEDON1 gene of Arabidopsis regulates shoot apical meristem formation. Development 128: 1127–1135

    Not in our library10.1242/dev.128.7.1127

  44. 44.

    To JP, Kieber JJ (2008 ) Cytokinin signaling: two-components and more. Trends Plant Sci. 13: 85–92

    Not in our library10.1016/j.tplants.2007.11.005

  45. 45.

    Venglat SP, Dumonceaux T, Rozwadowski K, Parnell L, Babic V, Keller W, Martienssen R, Selvaraj G, Datla R (2002 ) The homeobox gene BREVIPEDICELLUS is a key regulator of inflorescence architecture in Arabidopsis. Proc Natl Acad Sci USA 99: 4730–4735

    Not in our library10.1073/pnas.072626099

  46. 46.

    Vernoux T, Besnard F, Traas J (2010 ) Auxin at the shoot apical meristem. Cold Spring Harb Perspect Biol 2: a001487

    Not in our library10.1101/cshperspect.a001487

  47. 47.

    Wu G, Lin WC, Huang T, Poethig RS, Springer PS, Kerstetter RA (2008 ) KANADI1 regulates adaxial-abaxial polarity in Arabidopsis by directly repressing the transcription of ASYMMETRIC LEAVES2. Proc Natl Acad Sci USA 105: 16392–16397

    Not in our library10.1073/pnas.0803997105

  48. 48.

    Yadav RK, Girke T, Pasala S, Xie M, Reddy GV (2009 ) Gene expression map of the Arabidopsis shoot apical meristem stem cell niche. Proc Natl Acad Sci USA 106: 4941–4946

    Not in our library10.1073/pnas.0900843106

  49. 49.

    Yadav RK, Perales M, Gruel J, Girke T, Jönsson H, Reddy GV (2011 ) WUSCHEL protein movement mediates stem cell homeostasis in the Arabidopsis shoot apex. Genes Dev 25: 2025–2030

    Not in our library10.1101/gad.17258511

  50. 50.

    Yadav RK, Tavakkoli M, Reddy GV (2010 ) WUSCHEL mediates stem-cell homeostasis by regulating stem-cell number and patterns of cell division and differentiation of stem-cell progenitors. Development 137: 3581–3589

    Not in our library10.1242/dev.054973

  51. 51.

    Yamaguchi M, Ohtani M, Mitsuda N, Kubo M, Ohme-Takagi M, Fukuda H, Demura T (2010 ) VND-INTERACTING2, a NAC domain transcription factor, negatively regulates xylem vessel formation in Arabidopsis. Plant Cell 22: 1249–1263

    Not in our library10.1105/tpc.108.064048

  52. 52.

    Zhao DZ, Wang GF, Speal B, Ma H (2002 ) The excess microsporocytes1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther. Genes Dev 16: 2021–2031

    Not in our library10.1101/gad.997902

  53. 53.

    Zhao Z, Andersen SU, Ljung K, Dolezal K, Miotk A, Schultheiss SJ, Lohmann JU (2010 ) Hormonal control of the shoot stem-cell niche. Nature 465: 1089–1092

    Not in our library10.1038/nature09126

Cited by papers we hold 3

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.