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The primitive growth factor NME7AB induces mitochondrially active naive-like pluripotent stem cells.

ABSTRACT: Naïve pluripotent stem cells (PSCs) display a distinctive phenotype when compared to their "primed" counterparts, including, but not limited to, increased potency to differentiate and more robust mitochondrial respiration. The cultivation and maintenance of naïve PSCs have been notoriously challenging, requiring the use of complex cytokine cocktails. NME7AB is a newly discovered embryonic stem cell growth factor that is expressed exclusively in the first few days of human blastocyst development. It has been previously reported that growing primed induced PSCs (iPSCs) in bFGF-depleted medium with NME7AB as the only added growth factor facilitates the regression of these cells to their naïve state. Here, we confirm this regression by demonstrating the reactivation of mitochondrial function in the induced naïve-like PSCs and increased ATP production in these cells, as compared to that in primed iPSCs.

SUBMITTER: O'Reilly C

PROVIDER: S-EPMC6711853 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The primitive growth factor NME7<sub>AB</sub> induces mitochondrially active naïve-like pluripotent stem cells.

O'Reilly Carla C Qi Qian Q Peters Jennifer L JL Cheng Yong Y Yoon Sang-Oh SO Han Min-Joon MJ

Biochemistry and biophysics reports 20190820

Naïve pluripotent stem cells (PSCs) display a distinctive phenotype when compared to their "primed" counterparts, including, but not limited to, increased potency to differentiate and more robust mitochondrial respiration. The cultivation and maintenance of naïve PSCs have been notoriously challenging, requiring the use of complex cytokine cocktails. NME7<sub>AB</sub> is a newly discovered embryonic stem cell growth factor that is expressed exclusively in the first few days of human blastocyst d ...[more]

PMID: 31467990

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Project description:BackgroundHuman naïve pluripotency state cells can be derived from direct isolation of inner cell mass or primed-to-naïve resetting of human embryonic stem cells (hESCs) through different combinations of transcription factors, small molecular inhibitors, and growth factors. Long noncoding RNAs (lncRNAs) have been identified to be crucial in diverse biological processes, including pluripotency regulatory circuit of mouse pluripotent stem cells (PSCs), but few are involved in human PSCs' regulation of pluripotency and naïve pluripotency derivation. This study initially planned to discover more lncRNAs possibly playing significant roles in the regulation of human PSCs' pluripotency, but accidently identified a lncRNA whose knockdown in human PSCs induced naïve-like pluripotency conversion.MethodsCandidate lncRNAs tightly correlated with human pluripotency were screened from 55 RNA-seq data containing human ESC, human induced pluripotent stem cell (iPSC), and somatic tissue samples. Then loss-of-function experiments in human PSCs were performed to investigate the function of these candidate lncRNAs. The naïve-like pluripotency conversion caused by CCDC144NL-AS1 knockdown (KD) was characterized by quantitative real-time PCR, immunofluorescence staining, western blotting, differentiation of hESCs in vitro and in vivo, RNA-seq, and chromatin immunoprecipitation. Finally, the signaling pathways in CCDC144NL-AS1-KD human PSCs were examined through western blotting and analysis of RNA-seq data.ResultsThe results indicated that knockdown of CCDC144NL-AS1 induces naïve-like state conversion of human PSCs in the absence of additional transcription factors or small molecular inhibitors. CCDC144NL-AS1-KD human PSCs reveal naïve-like pluripotency features, such as elevated expression of naïve pluripotency-associated genes, increased developmental capacity, analogous transcriptional profiles to human naïve PSCs, and global reduction of repressive chromatin modification marks. Furthermore, CCDC144NL-AS1-KD human PSCs display inhibition of MAPK (ERK), accumulation of active β-catenin, and upregulation of some LIF/STAT3 target genes, and all of these are concordant with previously reported traits of human naïve PSCs.ConclusionsOur study unveils an unexpected role of a lncRNA, CCDC144NL-AS1, in the naïve-like state conversion of human PSCs, providing a new perspective to further understand the regulation process of human early pluripotency states conversion. It is suggested that CCDC144NL-AS1 can be potentially valuable for future research on deriving higher quality naïve state human PSCs and promoting their therapeutic applications.

Dataset Information

The primitive growth factor NME7AB induces mitochondrially active naive-like pluripotent stem cells.

Publications

The primitive growth factor NME7<sub>AB</sub> induces mitochondrially active naïve-like pluripotent stem cells.

Similar Datasets

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