Direct Isolation and RNA-seq Reveal Environment-dependent Properties of Engrafted Neural Stem/progenitor Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Oct 18

PMID 23072808

Citations 36

Authors

Hiromi Kumamaru

Yasuyuki Ohkawa

Hirokazu Saiwai

Hisakata Yamada

Kensuke Kubota

Kazu Kobayakawa

Koichi Akashi

Hideyuki Okano

Yukihide Iwamoto

Seiji Okada

Affiliations

Soon will be listed here.

Abstract

Neural stem/progenitor cell (NSPC) transplantation is a promising treatment for various neurodegenerative disorders including spinal cord injury, however, no direct analysis has ever been performed on their in vivo profile after transplantation. Here we combined bioimaging, flow-cytometric isolation and ultra-high-throughput RNA sequencing to evaluate the cellular properties of engrafted NSPCs. The acutely transplanted NSPCs had beneficial effects on spinal cord injury, particularly neuroprotection and neurohumoral secretion, whereas their in situ secretory activity differed significantly from that predicted in vitro. The RNA-sequencing of engrafted NSPCs revealed dynamic expression/splicing changes in various genes involved in cellular functions and tumour development depending on graft environments. Notably, in the pathological environment, overall transcriptional activity, external signal transduction and neural differentiation of engrafted NSPCs were significantly suppressed. These results highlight the vulnerability of engrafted NSPCs to environmental force, while emphasizing the importance of in situ analysis in advancing the efficacy and safety of stem cell-based therapies.

Citing Articles

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References

Amariglio N, Hirshberg A, Scheithauer B, Cohen Y, Loewenthal R, Trakhtenbrot L . Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 2009; 6(2):e1000029. PMC: 2642879. DOI: 10.1371/journal.pmed.1000029. View

Kaltschmidt B, Widera D, Kaltschmidt C . Signaling via NF-kappaB in the nervous system. Biochim Biophys Acta. 2005; 1745(3):287-99. DOI: 10.1016/j.bbamcr.2005.05.009. View

Negrini S, Gorgoulis V, Halazonetis T . Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010; 11(3):220-8. DOI: 10.1038/nrm2858. View

Lee J, Jeyakumar M, Gonzalez R, Takahashi H, Lee P, Baek R . Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nat Med. 2007; 13(4):439-47. DOI: 10.1038/nm1548. View

Mahalik T, Hahn W, Clayton G, Owens G . Programmed cell death in developing grafts of fetal substantia nigra. Exp Neurol. 1994; 129(1):27-36. DOI: 10.1006/exnr.1994.1144. View

Zawada W, Kirschman D, Cohen J, Heidenreich K, Freed C . Growth factors rescue embryonic dopamine neurons from programmed cell death. Exp Neurol. 1996; 140(1):60-7. DOI: 10.1006/exnr.1996.0115. View

Carpentier P, Palmer T . Immune influence on adult neural stem cell regulation and function. Neuron. 2009; 64(1):79-92. PMC: 2789107. DOI: 10.1016/j.neuron.2009.08.038. View

Saiwai H, Ohkawa Y, Yamada H, Kumamaru H, Harada A, Okano H . The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. Am J Pathol. 2010; 176(5):2352-66. PMC: 2861100. DOI: 10.2353/ajpath.2010.090839. View

Shimada M, Niida H, Zineldeen D, Tagami H, Tanaka M, Saito H . Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell. 2008; 132(2):221-32. DOI: 10.1016/j.cell.2007.12.013. View

10.

He C, Zhou F, Zuo Z, Cheng H, Zhou R . A global view of cancer-specific transcript variants by subtractive transcriptome-wide analysis. PLoS One. 2009; 4(3):e4732. PMC: 2648985. DOI: 10.1371/journal.pone.0004732. View

11.

Zhou Z, Peng X, Insolera R, Fink D, Mata M . Interleukin-10 provides direct trophic support to neurons. J Neurochem. 2009; 110(5):1617-27. PMC: 2737090. DOI: 10.1111/j.1471-4159.2009.06263.x. View

12.

Sofroniew M, Howe C, Mobley W . Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci. 2001; 24:1217-81. DOI: 10.1146/annurev.neuro.24.1.1217. View

13.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

14.

Michels J, Johnson P, Packham G . Mcl-1. Int J Biochem Cell Biol. 2004; 37(2):267-71. DOI: 10.1016/j.biocel.2004.04.007. View

15.

Cao Q, Howard R, Dennison J, Whittemore S . Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord. Exp Neurol. 2002; 177(2):349-59. DOI: 10.1006/exnr.2002.7981. View

16.

Jandial R, Snyder E . A safer stem cell: on guard against cancer. Nat Med. 2009; 15(9):999-1001. DOI: 10.1038/nm0909-999. View

17.

Al-Shahrour F, Minguez P, Tarraga J, Montaner D, Alloza E, Vaquerizas J . BABELOMICS: a systems biology perspective in the functional annotation of genome-scale experiments. Nucleic Acids Res. 2006; 34(Web Server issue):W472-6. PMC: 1538844. DOI: 10.1093/nar/gkl172. View

18.

Micci M, Pasricha P . Neural stem cells for the treatment of disorders of the enteric nervous system: strategies and challenges. Dev Dyn. 2006; 236(1):33-43. DOI: 10.1002/dvdy.20975. View

19.

Okada S, Ishii K, Yamane J, Iwanami A, Ikegami T, Katoh H . In vivo imaging of engrafted neural stem cells: its application in evaluating the optimal timing of transplantation for spinal cord injury. FASEB J. 2005; 19(13):1839-41. DOI: 10.1096/fj.05-4082fje. View

20.

Dobkin B, Curt A, Guest J . Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury. Neurorehabil Neural Repair. 2006; 20(1):5-13. PMC: 4169140. DOI: 10.1177/1545968305284675. View