# Generating morphogen gradients to engineer human integumentary organoids

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $202,500

## Abstract

Project Summary
 Recent success in generating human organoids from embryonic bodies (EBs) of induced pluripotent stem
cells (iPSCs) offers a new tool to understand human organ morphogenesis and genetic diseases. However, the
current organoid generating approaches, where cells are symmetrically exposed to differentiation
factors/morphogens in culture, only allow for the generation of partial components of a tissue, thereby do not
support the spatially-controlled generation of multicomponent tissues. The current challenge in organoid
research is to achieve a physiologically-relevant organization of cells, tissue components, and anatomical
features. In this project, we postulate that generating defined asymmetrical chemical gradients in EBs will lead
to controlled differentiation of iPSCs into multicomponent organoids comprising anatomical features. This
approach will overcome the current limitations of symmetrical culture conditions. The skin represents a great
model organ to test this hypothesis, because (i) the skin morphogenesis strongly relies on interactions of cells
from multiple lineages; and (ii) generation of hair follicles and pigmentation can be used as functional read-outs
to assess the robustness of this bioengineering approach, which can later be adapted for other organoid systems.
 In Specific Aim 1, we will generate precise cross-gradients of differentiation factors at the single EB level using
microfluidics. We postulate that this will induce simultaneous generation of epidermal cells and neural crest cell-
derived melanocytes and dermal papilla cells. Our success criteria will be the recapitulation of the early events
of skin morphogenesis, such as the formation of skin appendages and pigmentation of the epidermis. In Specific
Aim 2, we will extend this approach to model a genetic disease. We will focus on Hutchinson-Gilford progeria
syndrome (HGPS), which is a rare monogenic premature aging disease with distinct skin abnormalities including
sclerotic skin, dyspigmentation, and alopecia. We will first induce skin morphogenesis using patient iPSCs to
develop a skin disease phenotype. Subsequently, we will use our microphysiological skin model to identify early
developmental abnormalities in progeria skin, which are largely unknown for humans, and further evaluate the
efficacy and toxicity of three drugs with different molecular targets on the reversal of HGPS skin phenotype in a
human relevant-context. This innovative approach represents a critical step towards engineering fully-developed
integumentary organoids and will have an immediate and overwhelming impact on our understanding of human
skin morphogenesis and developmental skin diseases.

## Key facts

- **NIH application ID:** 10057882
- **Project number:** 1R21EB028970-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hasan Erbil Abaci
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057882

## Citation

> US National Institutes of Health, RePORTER application 10057882, Generating morphogen gradients to engineer human integumentary organoids (1R21EB028970-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057882. Licensed CC0.

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