Poly (A) binding protein 2 is critical for stem cell differentiation during regeneration in the planarian Schmidtea mediterranea

Namita Mukundan; Nivedita Hariharan; Vidyanand Sasidharan; Vairavan Lakshmanan; Dasaradhi Palakodeti; Colin Jamora

doi:10.3389/fcell.2024.1433142

Poly (A) binding protein 2 is critical for stem cell differentiation during regeneration in the planarian Schmidtea mediterranea

Front Cell Dev Biol. 2024 Sep 23:12:1433142. doi: 10.3389/fcell.2024.1433142. eCollection 2024.

Authors

Namita Mukundan^{1

2}, Nivedita Hariharan¹, Vidyanand Sasidharan³, Vairavan Lakshmanan¹, Dasaradhi Palakodeti^{1

2}, Colin Jamora^{1

4}

Affiliations

¹ Integrative Chemical Biology (ICB), Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India.
² Manipal Academy of Higher Education, Manipal, India.
³ Stowers Institute for Medical Research, Kansas City, MO, United States.
⁴ Department of Life Science, Shiv Nadar Institution of Eminence, Greater Noida, Uttar Pradesh, India.

Abstract

Post-transcriptional regulation has emerged as a key mechanism for regulating stem cell renewal and differentiation, which is essential for understanding tissue regeneration and homeostasis. Poly(A)-binding proteins are a family of RNA-binding proteins that play a vital role in post-transcriptional regulation by controlling mRNA stability and protein synthesis. The involvement of poly(A) binding proteins in a wide range of cellular functions is increasingly being investigated. In this study, we used the regenerative model planarian organism Schmidtea mediterranea to demonstrate the critical role of poly(A)-binding protein 2 (PABP2) in regulating neoblast maintenance and differentiation. A deficit in PABP2 blocks the transition of neoblasts toward immediate early progenitors, leading to an enhanced pool of non-committed neoblasts and a decreased progenitor population. This is reflected in variations in the transcriptome profile, providing evidence of downregulation in multiple lineages. Thus, an insufficiency of PABP2 resulted in defective formation and organization of tissue, leading to abnormal regeneration. Our study reveals the essential role of PABP2 in regulating genes that mediate stem cell commitment to early progenitors during tissue regeneration.

Keywords: differentiation; planaria; poly A binding protein; post transcriptional regulation; regeneration; stem cell.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. NM thanks the Institute for Stem Cell Science and Regenerative Medicine (inStem) for PhD fellowship funding. NH was supported by inStem core grant. VL was supported by the Council of Scientific and Industrial Research (CSIR)- SRF. VS was funded by the Stowers Institute for Medical Research. This project was funded by an inStem core grant and Department of Science and Technology (DST) -Swarnajayanti fellowship (DST/SJE/LSA-02/2015–16) to DP. Work in the CJ lab is supported by core funds from inStem and grants from the Government of Biotechnology of the Government of India (BT/PR8738/AGR/36/770/2013, BT/PR32539/BRB/10/1814/2019).