# Transcriptional Factor SOX2, LncRNA HBL1, microRNA1 and PRC2 Epigenetic Complex Compose a Network to Orchestrate Cardiac Differentiation from Human Pluripotent Stem Cells

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $488,573

## Abstract

PROJECT SUMMARY/ABSTRACT
During the past decades, studies of heart development have been mainly focused on conserved gene
regulatory mechanisms, which control various aspects of cardiogenesis across multiple species from
drosophila to mouse. These conserved gene programs include cardiac transcriptional factors (such as Nkx2.5,
Isl1, Tbx20), microRNAs, and epigenetic regulators. Despite the high evolutionary conservation of
cardiogenesis, the human heart exhibits unique properties, including distinctive morphogenesis and
electrophysiological properties. These species-specific differences suggest the existence of novel genetic
programs in each species. As the limitation of experimental setting, it remains unclear the mechanisms that
regulate unique aspects of human cardiogenesis, and how human-specific mechanisms interact with
conserved gene programs to fine-tune human heart development. Recently, accumulating evidence
demonstrated that long noncoding RNAs (lncRNAs) play important roles in cell fate specification and
organogenesis, including the heart. LncRNAs are greater than 200bp non-coding transcripts, which account for
>40% of human transcriptome. Many lncRNAs are tissue-specific and species-specific. Recently, we identified
a novel human-specific lncRNA, named Heart Brake LncRNA1 (HBL1) (Dev. Cell. 2017, 4:333-8). HBL1 is
highly expressed in both cytoplasm and nucleus of human induced pluripotent stem cells (hiPSCs). Cytosolic
HBL1 modulates cardiomyocyte (CM) development from hiPSCs by counteracting microRNA1 (MIR1).
Pluripotency marker gene SOX2 activates HBL1 transcription. In this proposal, we will analyze further, a novel
mechanism of nuclear HBL1 in initiating the cardiac gene-expressing program via interacting with polycomb
repressive complex 2 (PRC2). Additionally, we will test a hypothesis that HBL1 adds a new layer of human-
specific regulatory mechanism on top of a conserved cardiogenic axis. All together, the central hypothesis is
that transcriptional factor SOX2, lncRNA HBL1, microRNA-1 and PRC2 complex composite a whole network to
control human cardiogenesis from pluripotent stem cells.

## Key facts

- **NIH application ID:** 10242624
- **Project number:** 5R01HL147871-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Lei Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $488,573
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242624

## Citation

> US National Institutes of Health, RePORTER application 10242624, Transcriptional Factor SOX2, LncRNA HBL1, microRNA1 and PRC2 Epigenetic Complex Compose a Network to Orchestrate Cardiac Differentiation from Human Pluripotent Stem Cells (5R01HL147871-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242624. Licensed CC0.

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