# Identification of Novel Human LncRNAs Controlling Human Cardiogenesis

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $196,766

## Abstract

PROJECT SUMMARY / ABSTRACT
During the past decades, one major focus of heart developmental biology is on the cardiac transcriptional
factors (such as Nkx2.5, Isl1, Tbx20), which are conserved coding genes across multiple species and play key
roles in controlling cardiogenesis. However, human heart has different size, electrophysiological properties and
distinct cardiogenesis process from rodents. Why such species-specific differences exist and what gene
programs control human-specific cardiogenesis and heart function are still remaining unknown.
Recently, accumulating evidences showed that long noncoding RNAs (lncRNAs) play important roles in cell
fate specification and organ development. LncRNAs are > 200 nucleotides noncoding transcripts with limited
coding potential. LncRNAs account for ~40% of human transcriptome. Particularly, many lncRNAs are tissue-
specific and species-specific with poor interspecies conservations. Additionally, recent evidences
demonstrated dys-regulated lncRNAs could cause various cardiovascular diseases.
All these evidences allow us to hypothesize that lncRNAs are species-specific genes, which could regulate
human-specific cardiogenesis. In our preliminary studies, we recapitulated early human heart development
using human embryonic stem (ES) cells. By using whole transcriptome sequencing, we identified hundreds of
previously unannotated novel human lncRNAs, which showed lineage-specific expression patterns in human
ES cell-derived multipotential cardiovascular progenitor cells (MCPs), cardiomyocytes (CMs), smooth muscle
cells (SMs) or endothelial cells (ECs). To date, full sequences and functions of those novel human cardiac-
specific lncRNAs are still unknown. Therefore, in this proposal, we will conduct a screening to identify
functional novel human lncRNAs, which regulate MCP formation and/or commitment. Particularly, 21
unannotated lncRNAs, which are specifically enriched in human heart progenitor cells (MCPs) with high
abundance, were chosen as target lncRNA candidates. Given that some lncRNAs are partially overlapping with
host or neighbor genes, complete deletion of lncRNA using classic CRISPR/Cas-9 may partially delete its
host/neighbor genes. Thus, we decided to utilize a recently reported inducible CRISPR/Cas-9 interference
(CRISPRi) system to knock down lncRNAs without disturbing their host/neighbor genes. Meanwhile, an
inducible CRISPR/Cas-9 activation (CRISPRa) system will be utilized in this proposal to activate endogenous
lncRNA expression. Overall, by taking advantages of our in vitro model of human cardiogenesis in ES cells and
the cutting-edge technologies of CRISPRi/a, this proposal aims to define sequences and determine functions
of a list of novel human lncRNAs in regulating early human heart development.

## Key facts

- **NIH application ID:** 9857631
- **Project number:** 5R21HD095049-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Lei Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,766
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857631

## Citation

> US National Institutes of Health, RePORTER application 9857631, Identification of Novel Human LncRNAs Controlling Human Cardiogenesis (5R21HD095049-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857631. Licensed CC0.

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