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Location: Animal Biosciences & Biotechnology Laboratory

Title: Knockdown Brm and Baf170, components of chromatin remodeling complex, facilitates reprogramming of somatic cells

item JIANG, ZONGLIANG - University Of Connecticut
item TANG, YONG - University Of Connecticut
item ZHAO, XUEMING - University Of Connecticut
item Donovan, David
item TIAN, XIUCHUN - University Of Connecticut

Submitted to: Stem Cells and Development
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/29/2015
Publication Date: 10/1/2015
Citation: Jiang, Z., Tang, Y., Zhao, X., Donovan, D.M., Tian, X. 2015. Knockdown Brm and Baf170, components of chromatin remodeling complex, facilitates reprogramming of somatic cells. Stem Cells and Development. 24(19):2328-36.

Interpretive Summary: There is a need to develop technologies for improving livestock species and to verify and test the role of genes believed to contribute to economically important traits. Stem cells are part of a technology that is believed important to achieving this goal. Understanding these cells and the cellular processes involved in creating the stem cells might help make the process more readily accessible to interested scientists for further experimentation. In this work, mouse cells were subjected to a technology that reduces the expression of two genes that are believed to play a role in the creation of stem cells from mouse cells. The results identified an improved method for scientists interested in cresating mouse stem cells and increasing the frequency of obtaining them. This will benefit scientists studying this process and thus increase the potential for using stem cells to improve livestock species.

Technical Abstract: The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells (ESCs) esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. Here we sought to determine whether Brm and Baf170 play any roles in iPSC reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid and late stages (Days 3, 6 and 9 after initial iPSC induction) and knocking down Baf170 during late stage (Day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the “pluripotency circuitry” and by constituting to the Stat3-regulated epigenetic network during pluripotency establishment.