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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
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Osblr8 orchestrates intrachromosomal loop structure required for maintaining stem cell pluripotency.
Yanbo Zhu1, Zi Yan2,3, Zhonghua Du1
1Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Stem Cell and Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
International Journal of Biological Sciences
|May 14, 2020
Summary
A novel long noncoding RNA, Osblr8, is crucial for maintaining pluripotency in induced pluripotent stem cells (iPSCs). It modulates chromatin architecture to activate essential stem cell genes during reprogramming.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Genomics
Background:
- Induced pluripotent stem cells (iPSCs) hold promise for regenerative medicine due to their self-renewal and differentiation capabilities.
- Understanding the epigenetic mechanisms regulating pluripotency is key to harnessing iPSC therapeutic potential.
Purpose of the Study:
- To investigate the role of 3D genome architecture in activating endogenous pluripotency genes.
- To identify novel epigenetic factors involved in maintaining pluripotency.
Main Methods:
- Chromatin RNA in situ reverse transcription sequencing (CRIST-seq) was employed.
- Knockdown and overexpression studies of the identified long noncoding RNA (lncRNA) were performed.
Main Results:
- A novel lncRNA, Osblr8, was identified, binding Oct4 and Sox2 and highly expressed in pluripotent cells.
- Osblr8 is essential for maintaining pluripotency and activates stem cell core factors upon overexpression.
- Osblr8 facilitates intrachromosomal looping to activate stem cell factors during reprogramming.
Conclusions:
- The lncRNA Osblr8 acts as a chromatin architecture modulator for pluripotency gene promoters.
- Osblr8 plays a critical epigenetic role in the reprogramming process and maintenance of pluripotency.
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