TET2 haploinsufficiency alters reprogramming into induced pluripotent stem cells

Lise Secardin, Cintia Elisabeth Gomez Limia, Antonio di Stefano, Martin Hernan Bonamino, Joseph Saliba, Keisuke Kataoka, Stevens K. Rehen, Hana Raslova, Caroline Marty, Seishi Ogawa, William Vainchenker, Barbara da Costa Reis Monte-Mor, Isabelle Plo

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


The discovery of the Ten-Eleven Translocation (TET) protein family was initiated by the identification of the MLL partner TET1, and of mutations in the TET2 gene in hematological malignancies including myeloproliferative neoplasms (MPN). TET1, 2 and 3 proteins hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and further oxidize 5-hmC into 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Previous studies highlight the involvement of TET proteins in somatic cells reprogramming into induced pluripotent stem cells (iPSC), particularly Tet1 and 2 in mouse and TET1 in human. Here, we asked whether endogenous TET2 knockdown also displays this function. Using different shRNA against TET2, we provide evidence that TET2 strongly decreases the reprogramming of human hematopoietic progenitor cells into iPSC. Importantly, using 2 MPN patients, we observed that TET2 mutations affecting catalytic domain allowed iPSC generation. Instead, using another TET2 and TET3-mutated patient, we could only reprogram IPSC with TET3 mutation alone, suggesting that the type of TET2 mutation and/or the cooperation with TET3 mutations may alter the reprogramming activity. Altogether, this work highlights the importance of endogenous TET in the reprogramming process of human hematopoietic progenitors.

Original languageEnglish
Article number101755
JournalStem Cell Research
Publication statusPublished - 2020 Apr
Externally publishedYes


  • 5-hmC, iPSC
  • Reprogramming
  • TET2

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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