Stemgent Stemolecule All-Trans Retinoic Acid

Stemolecule All-Trans Retinoic Acid is the oxidized form of Vitamin A and functions as a signaling molecule for various developmental pathways that control differentiation and proliferation^1,2. It acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid × receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions activating gene transcription³. All-Trans Retinoic Acid has been implicated in specification of the embryonic anterior/posterior axis through Hox gene regulation⁴. It has been used in various differentiation protocols, including B-cells, T-cells and neurons and applied clinically to treat cancer as a form of differentiation-induction therapy^2,5-11.

Product Name

Stemolecule All-Trans Retinoic Acid

Catalog Number

04-0021

Size

100 mg

Alternate Name(s)

• ATRA
• (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid

Chemical Formula

C₂₀H₂₈O₂

Molecular Weight

300.44

CAS Number

302-79-4

Purity

Greater than 98% by HPLC analysis

Formulation

Yellow to light orange crystalline powder

Solubility

For a 10 mM concentrated stock solution of All-Trans Retinoic Acid, add 1.66mL of DMSO to 5mg of the compound. If a precipitate is observed, warm the solution to 37°C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 100 mM and 95% ethanol at 9 mM.

Storage and Stability

Store powder at 4°C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20°C. The effect of storage of stock solutions should be verified for each application.

Quality Control

The purity of All-Trans Retinoic Acid was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of All-Trans Retinoic Acid was tested on mouse embryonic stem cells.

Specification Sheets

• 04-0021 Specifications Sheet

Safety Data Sheets

• 04-0021 Safety Data Sheet

1. Duester, G. Retinoic acid synthesis and signaling during early organogenesis. Cell 134: 921-931 (2008).
2. Ertesvåg, A., Naderi, S., Blomhoff, H.K. Regulation of B cell proliferation and differentiation by retinoic acid. Semin Immunol 21: 36-41 (2009).
3. Marshall, H., Morrison, A., Studer, M., Pöpperl, H. and Krumlauf, R. Retinoids and Hox genes. FASEB J 10: 969-978 (1996).
4. Holland, L.Z. Developmental biology: a chordate with a difference. Nature 447: 153-155 (2007).
5. Yagi, J., Uchida, T., Kuroda, K., and Uchiyama, T. Influence of retinoic acid on the differentiation pathway of T-cells in the thymus. Cell Immunol 181: 153-162 (1997).
6. Dhara, S.K., and Stice, S.L. Neural differentiation of human embryonic stem cells. J Cell Biochem 105: 633-640 (2008).
7. Sasai, Y. Generation of dopaminergic neurons from embryonic stem cells. J Neurol 249 Suppl 2: II41-1144 (2002).
8. Takahashi, J., Palmer, T.D., and Gage, F.H. Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures. J Neurobiol 38: 65-81 (1999).
9. Wichterle, H., Lieberam, I., Porter, J.A., and Jessell, T.M. Directed differentiation of embryonic stem cells into motor neurons. Cell 110: 385-397 (2002).
10. Collins, S.J. Retinoic acid receptors, hematopoiesis and leukemogenesis. Curr Opin Hematol 15: 346-351 (2008).
11. Mongan, N.P., and Gudas, L.J. Diverse actions of retinoid receptors in cancer prevention and treatment. Differentiation 75: 853-870 (2007).

Additional Publications

• Gonzàlez BJ; Zhao H; Niu J; Williams DJ; Lee J; Goulbourne CN' Xing Y; Wang Y' Oberholzer J; Blumenkrantz MH; Chen X; LeDuc CA; Chung WK; Colecraft HM; Gromada J; ShenY; Goland RS; Leibel RL; Egli D. Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency. Commun Biology 5:779 (2022).
• Feng X; Cheng X-T; Zheng P; Li Y; Hakim J; Zhang SQ; Anderson SM; Linask K; Presti R; Zou J; Sheng Z-H; Blackstone c. Ligand-free mitochondria-localized mutant AR-induced cytotoxicity in spinal bulbar muscular atrophy. Brain awac269:doi.org/10.1093/brain/awac269 (2022).
• SIM EZ; Enomoto T; Shiraki N; Furuta N; Kashio S; Kambe T; Tsuyama T; Arakawa A; Ozawa H; Yokoyama M; Miuri M; Kume S. Methionine metabolism regulates pluripotent stem cell pluripotency and differentiation through zinc mobilization. Cell Rep 40:111120 (2022).
• Timilsina S; Kirsch-Mangu T; Werth S; Shepard B; Ma T; Villa-Diaz LG. Enhanced self-renewal of human pluripotent stem cells by simulated microgravity. npj Microgravity 8:22 (2022).
• Tan JJ; Guyette JP; Miki K; Xiao L Kaur G; Wu T; Zhu L; Hansen KJ; Ling K-H; Milan DJ; Ott HC. Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro. Nature Commun 12:4997 (2021).
• Ma S; Viola R: Sui L; Cherubini V; Barbetti F; Eigli D. β Cell Replacement after Gene Editing of a Neonatal Diabetes-Causing Mutation at the Insulin Locus. Stem Cell Reports https://doi.org/10.1016/j.stemcr.2018.11.006: (2018).
• Sun X; Song J; Huang H; Chen H; Qian K. Modeling hallmark pathology using motor neurons derived from the family and sporadic amyotrophic lateral sclerosis patient-specific iPS cells. Stem Cell Res Therapy 9:315 (2018).
• Yamashita T; Miyamoto T; Bando T; Ono T; Kobayashi S; Doi A;  Araki T; Kato Y; Shirakawa T; Suzuki Y; Yamauchi J; Yoshida S; Sato N. Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells. PLoS ONE 12:e171947 (2017).
• Pellett S; Tepp WH; Johnson EA; Sesardic D;. Assessment of ELISA as endpoint in neuronal cell-based assay for BoNT detection using hiPSC derived neurons. J Pharmacol Toxicol Methods 88:1-6 (2017).
• Zhu S; Russ HA; Wang X; Zhang M; Ma T; Xu T; Tang S; Hebrok M; Deng S. Human pancreatic β-like cells converted from fibroblasts. Nature Commun 7:10080 (2016).
• Han Y-C, Lim Y; Duffieldl MD; Liu J; Manaph NPA; Yang M; Keating DJ; Zhou X-F. Direct reprogramming of mouse fibroblasts to neural stem cells by small molecules. Stem Cells International 2016:4304916 (2016).
• Ogaki S; Morooka M; Otera K; Kume S. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent cells. Sci Rep5:17297 (2015).
• Suissa Y; Magenheim J; Stolovich-Rain M; Hija A; Collombat P; Mansouri A; Sussel L; Sosa-Pineda L; McCracken K; Wells JM; Heller RS; Dor Y; Glaser B. Gastrin: A Distinct Fate of Neurogenin3 Positive Progenitor Cells in the Embryonic Pancreas. PLoS One 8(8): (2013)
• Ouglane R; Lando D; Jonson I; Dahl JA; Moen MN; Nordstrand LM; Rognes T; Lee JT; Klungland A; Kouzarides T; Larsen E. ALKBH1 is a histone H2A dioxygenase involved in neural differentiation. Stem Cells30:2672 (2012).