Amazing stuff! Just blogged here about another study covering dedifferentiation and even redifferentiation in context of a heart attack!
"... The researchers discovered that a transcription factor called ZBTB12 was involved in hPSC differentiation, the first time that ZBTB12 had been reported as being involved in the differentiation process. Transcription factors (TFs) are involved in the conversion (transcription) of DNA into RNA and are vital to controlling gene expression.
Undertaking single-cell RNA sequencing, they found that ZBTB12 inhibits dedifferentiation. hPSCs [human pluripotent stem cells] with a deficiency of ZBTB12 dedifferentiated into more primitive stem cells. They were prevented from differentiating into a more advanced form, confirming that the ZBTB12 gene is essential to stem cell differentiation.
... the researchers found that ZBTB12 is key in inhibiting the expression of human endogenous retrovirus H (HERVH). Comprising about 8% of the human genome, human endogenous retroviruses are “fossil viruses” found on DNA, relics of ancient infections transmitted along primates’ germlines over millions of years. ..."
From the abstract:
"Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition of cell fates remain largely unknown. Through exact transcription start site mapping, we report an evolutionarily conserved BTB domain-containing zinc finger protein, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single-cell RNA sequencing reveals that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 fine-tunes the expression of human endogenous retrovirus H (HERVH), a primate-specific retrotransposon, and targets specific transcripts that utilize HERVH as a regulatory element. In particular, the downregulation of HERVH-overlapping long non-coding RNAs (lncRNAs) by ZBTB12 is necessary for a successful exit from a pluripotent state and lineage derivation. Overall, we identify ZBTB12 as a molecular barrier that safeguards the unidirectional transition of metastable stem cell fates toward developmentally advanced states."
Fig. 1: nanoCAGE identifies a new pluripotency regulator ZBTB12
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