Direct conversion of fibroblasts to functional neurons by defined factors

Vierbuchen, Thomas; Ostermeier, Austin; Pang, Zhiping P.; Kokubu, Yuko; Südhof, Thomas C.; Wernig, Marius
February 2010
Nature;2/25/2010, Vol. 463 Issue 7284, p1035
Academic Journal
Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.


Related Articles

  • Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Moon, Jai-Hee; Heo, June Seok; Kim, Jun Sung; Jun, Eun Kyoung; Lee, Jung Han; Kim, Aeree; Kim, Jonggun; Whang, Kwang Youn; Kang, Yong-Kook; Yeo, Seungeun; Lim, Hee-Joung; Han, Dong Wook; Kim, Dong-Wook; Oh, Sejong; Yoon, Byung Sun; Schöler, Hans R; You, Seungkwon // Cell Research;Sep2011, Vol. 21 Issue 9, p1305 

    Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into...

  • Reprogramming to Pluripotency through a Somatic Stem Cell Intermediate. Marthaler, Adele G.; Tiemann, Ulf; Araúzo-Bravo, Marcos J.; Wu, Guangming; Zaehres, Holm; Hyun, Jung Keun; Han, Dong Wook; Schöler, Hans R.; Tapia, Natalia // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Transcription factor-based reprogramming can lead to the successful switching of cell fates. We have recently reported that mouse embryonic fibroblasts (MEFs) can be directly reprogrammed into induced neural stem cells (iNSCs) after the forced expression of Brn4, Sox2, Klf4, and Myc. Here, we...

  • De-Differentiation of Mouse Interfollicular Keratinocytes by the Embryonic Transcription Factor Oct-4. Grinnell, Katie L.; Yang, Baoli; Eckert, Richard L.; Bickenbach, Jackie R. // Journal of Investigative Dermatology;Feb2007, Vol. 127 Issue 2, p372 

    The embryonic transcription factor Oct-4 is often referred to as the master regulator of the undifferentiated state. Although its role in maintaining embryonic stem (ES) cell pluripotency is well established, its ability to directly reprogram committed somatic cells is not well defined. Using...

  • Imaging: Visualizing a neuronal handshake. Miyawaki, Atsushi // Nature Chemical Biology;Dec2010, Vol. 6 Issue 12, p885 

    The article reports that the interaction of the neuronal cell surface adhesion proteins neurexin and neuroligin is improved at synapses when there is motivation or developmental activity. It says that increased activity-dependent surface density of neurexin-neuroligin complexes is required for...

  • The Snail Transcription Factor Regulates the Numbers of Neural Precursor Cells and Newborn Neurons throughout Mammalian Life. Zander, Mark A.; Cancino, Gonzalo I.; Gridley, Thomas; Kaplan, David R.; Miller, Freda D. // PLoS ONE;Aug2014, Vol. 9 Issue 8, p1 

    The Snail transcription factor regulates diverse aspects of stem cell biology in organisms ranging from Drosophila to mammals. Here we have asked whether it regulates the biology of neural precursor cells (NPCs) in the forebrain of postnatal and adult mice, taking advantage of a mouse containing...

  • DNA-binding factors shape the mouse methylome at distal regulatory regions. Stadler, Michael B.; Murr, Rabih; Burger, Lukas; Ivanek, Robert; Lienert, Florian; Schöler, Anne; Wirbelauer, Christiane; Oakeley, Edward J.; Gaidatzis, Dimos; Tiwari, Vijay K.; Schübeler, Dirk // Nature;12/22/2011, Vol. 480 Issue 7378, p490 

    Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced...

  • Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency. Hester, Mark E.; SungWon Song; Miranda, Carlos J.; Eagle, Amy; Schwartz, Phillip H.; Kaspar, Brian K. // PLoS ONE;2009, Vol. 4 Issue 9, p1 

    Background: Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been...

  • Id proteins sustain Hes1 expression to maintain neural stem cells. Ge Bai; Nengyin Sheng; Zhihui Xie; Wei Bian; Yokota, Yoshifumi; Benezra, Robert; Kageyama, Ryoichiro; Guillemot, Francois; Naihe Jing // Cell Research;Aug2008 Supplement, Vol. 18, pS19 

    Negative bHLH transcription factor Hes1 can inhibit neural stem cells (NSCs) from precocious neurogenesis through repressing proneural gene expression; therefore, sustenance of Hes1 expression is crucial for NSC pool maintenance. Here, we find that Ids, the dominant-negative regulators of...

  • Neurobiology: Keeping a lid on it. Turrigiano, Gina // Nature;7/17/2014, Vol. 511 Issue 7509, p297 

    The article discusses the role of activity dependent transcription factor Npas4 protein in inhibitory neurons promoting their activity. Topics discussed include coordination of gene expression pathways to the function of inhibitory and excitatory motifs, activation Npas4 due to enhanced neuronal...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics