# The reprogramming of limb progenitor cells

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $415,524

## Abstract

ABSTRACT
This work is a continuation of our long-standing efforts to understand the formation of the vertebrate limb. The
hope is that the knowledge we glean will ultimately provide insights into the developmental defects leading to
congenital malformations and to novel regenerative therapies to restore injured appendages. While
replacement of developed limb tissues could, in principle, be achieved by harnessing and enhancing the
endogenous regenerative potential of the limb through a process akin to amphibian limb regeneration, an
alternative approach is to attempt to recapitulate embryonic limb development in an adult setting. Towards that
end, in preliminary studies, we have taken a reprogramming approach. Screening for a cocktail of transcription
factors capable of respecifying mesenchymal cells to a limb progenitor identity, we have evidence that Lhx2,
Nmyc, Sall4 and PDRM16 together can convert non-limb fibroblasts into cells with the properties of early limb
bud cells, including driving expression of a gene profile mimicking that is seen in the early limb bud, and can
imbue cells with the potential to differentiate into the range of cell types found in the developing limb. In Aim 1,
we will characterize these cells in greater detail in vitro to determine how closely they approximate endogenous
limb bud progenitors. In Aim 2, we will interrogate these cells functionally, testing their capacity to form
appropriate tissues and structures in vivo. Finally, in Aim 3, we will focus on two of the factors required for
putatively reprogramming limb bud progenitor cells, Sall4 and Lhx2, investigating whether they act through the
same sets of gene targets during reprogramming as they do during limb bud development. Together, these
studies will bring us closer to understanding how to manipulate limb-like cells for regenerative purposes and
will also potentially provide new insights into how early limb bud is regulated.

## Key facts

- **NIH application ID:** 9939622
- **Project number:** 5R01HD032443-24
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** CLIFFORD J. TABIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,524
- **Award type:** 5
- **Project period:** 1995-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939622

## Citation

> US National Institutes of Health, RePORTER application 9939622, The reprogramming of limb progenitor cells (5R01HD032443-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939622. Licensed CC0.

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