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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Stem Cell Research

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1474631

This article is part of the Research Topic Advancements in Hematopoietic Stem Cell Proliferation and Self-Renewal Maintenance View all 6 articles

TAL1 Overexpression in Induced Pluripotent Stem Cells Promotes the Formation of Hematopoietic Cell Forming Complexes but Inhibits Enucleation in vitro

Provisionally accepted
Arim Shin Arim Shin Sung Ah Park Sung Ah Park Ji Yeon Kim Ji Yeon Kim Eun Jung Baek Eun Jung Baek *
  • Hanyang University, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    The in vitro generation of human red blood cells (RBCs) from stem cells, such as induced pluripotent stem cells (iPSCs), holds promise for transfusable RBCs but faces challenges, including RBC maturation, enucleation, and large-scale production. In this study, we evaluated the effect of conditional TAL1 overexpression on in vitro RBC production via hematopoietic cellforming complex (HCFC) formation from iPSCs since TAL1 is a key regulatory transcription factor essential for erythropoiesis. TAL1 overexpression in iPSCs, either before or after hematopoietic induction, significantly enhanced HCFC formation and hematopoietic differentiation, as evidenced by increased hematopoiesis-related gene expression, a higher yield of glycophorin A (GPA)+/CD71+ cells, and elevated gamma hemoglobin levels. These findings highlight the potential of TAL1 as a powerful regulator of erythropoiesis in vitro and offer a promising strategy for improving RBC production from stem cells. However, the reduced enucleation efficiency observed after TAL1 overexpression indicates a key challenge that must be addressed to optimize the generation of fully functional, transfusable RBCs. Further research is required to balance the benefits of enhanced differentiation with the need for efficient enucleation, which is critical for the production of mature, viable RBCs.

    Keywords: Induced Pluripotent Stem Cells, In vitro erythropoiesis, hematopoietic cell forming complex, enucleation, TAL1

    Received: 02 Aug 2024; Accepted: 21 Mar 2025.

    Copyright: © 2025 Shin, Park, Kim and Baek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Eun Jung Baek, Hanyang University, Seoul, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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