# Reprogramming of human dermal fibroblasts into inductive dermal papilla cells

> **NIH NIH R21** · UNIVERSITY OF CINCINNATI · 2022 · $176,418

## Abstract

Hair follicle (HF) regeneration has received great attention in the last decades due to increased demands for
effective cures for many diseases that involve hair loss and skin injuries. The challenges met in current
pharmacological and surgical approaches have provoked the efforts in developing more effective therapeutic
solutions. Cell-based bioengineering of HFs emerges as a promising strategy to overcome the hurdles in
regenerating HFs and achieve a “hairy” feat. The main obstacle is our inability to isolate and propagate human
dermal papilla (DP) fibroblasts with inductive capabilities, which are the major mesenchymal cells instructing
keratinocytes to build the HF structure. Although DP fibroblasts are known to constitute a dermal niche right at
the base of the HF, isolation of human DP fibroblasts from HFs is proven to be technically difficult and inefficient.
Isolated DP fibroblasts proliferate slowly under normal culture conditions due to missing key epithelial and
microenvironmental cues. Furthermore, human DP fibroblasts quickly lose hair inductivity during ex vivo
expansion and fail to produce HFs. The anatomical proximity and shared origin between dermal fibroblasts and
DP fibroblasts suggest that dermal fibroblasts may represent a viable option for supplying a large number of
inductive DP fibroblasts. However, dermal fibroblasts have not been explored whether they can be
reprogrammed to possess DP hair inductivity for HF bioengineering. Our long-term goal is to develop novel
bioengineering approaches to produce fully functional human HFs for clinical procedures. Using a three-
dimensional (3D) composite spheroid model, we found that the hair inductivity of human DP fibroblasts is greatly
improved and leads to the formation of HF-like structure. Furthermore, we identified five major transcription
factors (TFs) that are central to DP phenotype and inductivity. Our central hypothesis is that the DP phenotype
can be driven in human dermal fibroblasts (DFs) by activating master DP-TFs, thus reprogramming non‐hairy
epidermis to a follicular fate. In the first aim, we will determine whether human dermal fibroblasts can be
reprogrammed to establish DP characteristics and hair inductivity. We will activate the expression of five major
DP inductivity-related TFs in human DFs using a CRISPR activation system. Furthermore, we will identify which
TF has the highest transcriptional activity in reprogramming human dermal fibroblasts to initiate DP gene
expression, DP-keratinocyte interaction, and DP HF inductivity. In the second aim, we will determine whether
reprogrammed dermal fibroblasts in composite spheroids can induce HFs in ESS. We will use a combination of
3D composite spheroid and premade micropores to create an inductive niche in ESS. This work will provide a
new and in-depth understanding of novel mechanistic knowledge regarding genetic programs that are critical to
promoting DP characteristics and HF morphogenesis. The outcomes are sign...

## Key facts

- **NIH application ID:** 10391555
- **Project number:** 5R21AR078976-02
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Yuhang Zhang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $176,418
- **Award type:** 5
- **Project period:** 2021-04-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10391555

## Citation

> US National Institutes of Health, RePORTER application 10391555, Reprogramming of human dermal fibroblasts into inductive dermal papilla cells (5R21AR078976-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10391555. Licensed CC0.

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