Chapter 4: Chemical Transdifferentiation

Regenerative medicine, which can replace lost or damaged cells in a variety of tissues and organs, requires sufficient amounts of the desired competent cells for transplantation. Such cells can be obtained by the reprogramming of somatic cells into pluripotent stem cells (PSCs), which are then differentiated into the desired functional cells. However, transdifferentiation, which refers to direct lineage reprogramming of one specialized somatic cell type into another without passing through the pluripotent state, holds several advantages over the PSC based strategies, including higher efficiency and improved safety.

Changes in cellular fate involve a profound change in gene transcription, which is regulated predominantly by TFs. Thus, forced expression of tissue specific TFs was used to induce transdifferentiation of a variety of somatic cells within the same germ layer, and later, further development enabled transdifferentiation even across germ layers.

Small molecules were used initially to boost and facilitate TF-based transdifferentiation. However, further development in the field enabled transdifferentiation of various cell types using a mixture of small molecules and growth factors together with transient overexpression of the Yamanaka OSKM TFs (in contrast to the prolonged continuous forced expression of these TFs required for inducing pluripotency).

Recently, it was shown that it is possible to avoid completely the use of TFs in the transdifferentiation process by using a defined combination of small molecules and growth factors, a breakthrough that is in the development path still needed for regenerative medicine to realize its therapeutic potential.

List of Small Molecules

(Click to Enlarge)

Click to download Booklet

Click to download Flyer

References:

  1. Ebrahimi, (2016). Chemical-only reprogramming to pluripotency. Frontiers in Biology, 11(2), 75-84.
  2. Hou, , Li, Y., Zhang, X., et al., & Deng, H. (2013). Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science, 341(6146), 651-654.
  3. Lin, , & Wu, S. (2015). Reprogramming with small molecules instead of exogenous transcription factors. Stem cells international, 2015.
  4. Takahashi, , & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Сell, 126(4), 663-676.
  5. Zhang, , Li, W., Laurent, T., & Ding, S. (2012). Small molecules, big roles–the chemical manipulation of stem cell fate and somatic cell reprogramming. J Cell Sci, 125(23), 5609-5620.
Share This