HYBRID EVENT: You can participate in person at London, UK or Virtually from your home or work.

3rd Edition of International Conference on Tissue Engineering and Regenerative Medicine

August 21-23, 2023

August 21 -23, 2023 | London, UK
TERM C 2022

Mohan Malleshaiah

Mohan Malleshaiah, Speaker at TERM C 2022 Conferences
Montreal Clinical Research Institute, Canada
Title : Altering stem cell states by controlling cell signaling information

Abstract:

Cell fate determination induced by cell signaling is central to stem cells and regenerative medicine. Pluripotent stem cells such as embryonic stem cells (ESC) are an attractive model for understanding the relationship between cell signaling and cell fates. Cultured mouse ESCs are heterogeneous and can exist in multiple cell states such as Totipotent, Pluripotent, Primed and Primitive Endoderm. Such heterogeneity can compromise stem cell applications. The signaling mechanisms regulating the Totipotent state acquisition and coexistence of these multiple cell states are poorly understood. In this study, we identify BMP4 as an inducer of the Totipotent state. However, we discovered that BMP4-mediated induction of the Totipotent state is constrained by the cross-activation of FGF, TGF-b and WNT pathways. We exploited this finding to enhance the proportion of Totipotent cells in ESCs by rationally inhibiting the cross-activated pathways using small molecules. Next, we utilized single-cell mRNA-sequencing (scRNA-seq) to analyze the resulting impact on cellular heterogeneity. The scRNA-seq analysis revealed that induction of the Totipotent state is accompanied by the suppression of both the Primed and Primitive Endoderm states, thus reducing the overall stem cell heterogeneity. Furthermore, the reprogrammed Totipotent cells generated in culture have a molecular and functional resemblance to Totipotent cell stages of the preimplantation embryo. Our findings reveal a BMP4 signaling mechanism in ESCs to regulate multiple cell states, potentially significant for managing stem cell heterogeneity in differentiation and reprogramming.

Biography:

Dr. Mohan Malleshaiah studied Biotechnology at the Bangalore University, India and graduated as MS in 2002. He then worked for two years in the field of drug discovery at Aurigene Discovery Technologies. Inspired to pursue research, he then obtained PhD degree from the University of Montreal, Canada, in the field of Biochemistry. After postdoctoral fellowship at the Harvard Medical School, USA, he started independent research career in 2018 as an Assistant Professor at the Montreal Clinical Research Institute (IRCM) in affiliation with the University of Montreal. Dr. Malleshaiah lab works on stem cells, cell reprogramming, disease modelling and pancreatic cancer.

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