Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2014 Dec 3

PMID 25454632

Citations 24

Authors

John P Cassady

Ana C DAlessio

Sovan Sarkar

Vardhan S Dani

Zi Peng Fan

Kibibi Ganz

Reinhard Roessler

Mriganka Sur

Richard A Young

Rudolf Jaenisch

Affiliations

Soon will be listed here.

Abstract

Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors.

Citing Articles

RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1.

Choi W, Choe M, Kim S, Kim S, Lee J, Lee Y Cell Mol Life Sci. 2024; 81(1):99.

PMID: 38386071 PMC: 10884155. DOI: 10.1007/s00018-024-05129-y.

Targeted deletion of von-Hippel-Lindau in the proximal tubule conditions the kidney against early diabetic kidney disease.

Kunke M, Knofler H, Dahlke E, Zanon Rodriguez L, Bottner M, Larionov A Cell Death Dis. 2023; 14(8):562.

PMID: 37626062 PMC: 10457389. DOI: 10.1038/s41419-023-06074-7.

Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions.

Messerschmidt V, Chintapula U, Bonetesta F, Laboy-Segarra S, Naderi A, Nguyen K Front Physiol. 2022; 13:819767.

PMID: 35283767 PMC: 8906778. DOI: 10.3389/fphys.2022.819767.

Direct Neuronal Reprogramming: Bridging the Gap Between Basic Science and Clinical Application.

Vasan L, Park E, David L, Fleming T, Schuurmans C Front Cell Dev Biol. 2021; 9:681087.

PMID: 34291049 PMC: 8287587. DOI: 10.3389/fcell.2021.681087.

Five transcriptional factors reprogram fibroblast into myogenic lineage cells via paraxial mesoderm stage.

Hwang M, Lee E, Chung M, Park S, Jeong K Cell Cycle. 2020; 19(14):1804-1816.

PMID: 32579865 PMC: 7469637. DOI: 10.1080/15384101.2020.1780384.

References

Hardy R, Hayakawa K . B cell development pathways. Annu Rev Immunol. 2001; 19:595-621. DOI: 10.1146/annurev.immunol.19.1.595. View

Yang N, Zuchero J, Ahlenius H, Marro S, Ng Y, Vierbuchen T . Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol. 2013; 31(5):434-9. PMC: 3677690. DOI: 10.1038/nbt.2564. View

Bylund M, Andersson E, Novitch B, Muhr J . Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci. 2003; 6(11):1162-8. DOI: 10.1038/nn1131. View

Xie H, Ye M, Feng R, Graf T . Stepwise reprogramming of B cells into macrophages. Cell. 2004; 117(5):663-76. DOI: 10.1016/s0092-8674(04)00419-2. View

Okabe S, Forsberg-Nilsson K, Spiro A, Segal M, McKay R . Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech Dev. 1996; 59(1):89-102. DOI: 10.1016/0925-4773(96)00572-2. View

Ellis P, Fagan B, Magness S, Hutton S, Taranova O, Hayashi S . SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. Dev Neurosci. 2005; 26(2-4):148-65. DOI: 10.1159/000082134. View

Jung D, Giallourakis C, Mostoslavsky R, Alt F . Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006; 24:541-70. DOI: 10.1146/annurev.immunol.23.021704.115830. View

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

Glaser T, Pollard S, Smith A, Brustle O . Tripotential differentiation of adherently expandable neural stem (NS) cells. PLoS One. 2007; 2(3):e298. PMC: 1808430. DOI: 10.1371/journal.pone.0000298. View

10.

Cahoy J, Emery B, Kaushal A, Foo L, Zamanian J, Christopherson K . A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008; 28(1):264-78. PMC: 6671143. DOI: 10.1523/JNEUROSCI.4178-07.2008. View

11.

Elkabetz Y, Panagiotakos G, Al Shamy G, Socci N, Tabar V, Studer L . Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage. Genes Dev. 2008; 22(2):152-65. PMC: 2192751. DOI: 10.1101/gad.1616208. View

12.

Jaenisch R, Young R . Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 2008; 132(4):567-82. PMC: 4142810. DOI: 10.1016/j.cell.2008.01.015. View

13.

Wernig M, Meissner A, Cassady J, Jaenisch R . c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell. 2008; 2(1):10-2. DOI: 10.1016/j.stem.2007.12.001. View

14.

Brambrink T, Foreman R, Welstead G, Lengner C, Wernig M, Suh H . Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell. 2008; 2(2):151-9. PMC: 2276627. DOI: 10.1016/j.stem.2008.01.004. View

15.

Hanna J, Markoulaki S, Schorderet P, Carey B, Beard C, Wernig M . Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell. 2008; 133(2):250-64. PMC: 2615249. DOI: 10.1016/j.cell.2008.03.028. View

16.

Mikkelsen T, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P . Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008; 454(7200):49-55. PMC: 2754827. DOI: 10.1038/nature07056. View

17.

Wernig M, Lengner C, Hanna J, Lodato M, Steine E, Foreman R . A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 2008; 26(8):916-24. PMC: 2654269. DOI: 10.1038/nbt1483. View

18.

Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni J, Gygi S . Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 2009; 460(7259):1154-8. PMC: 2754867. DOI: 10.1038/nature08262. View

19.

Vierbuchen T, Ostermeier A, Pang Z, Kokubu Y, Sudhof T, Wernig M . Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010; 463(7284):1035-41. PMC: 2829121. DOI: 10.1038/nature08797. View

20.

Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R . Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci. 2010; 30(9):3489-98. PMC: 6634119. DOI: 10.1523/JNEUROSCI.4987-09.2010. View