# Deconstructing human body plan development with stem cells

> **NIH NIH K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $115,579

## Abstract

How the precise patterns are achieved during development of the human body plan remains obscure due to
limited access to human embryos, while elucidating the mechanisms will advance knowledge of human
development and contribute to regenerative medicine. The goal of my research is to reconstruct development of
the human body axis and appendages using pluripotent stem cells (iPSC) and to illuminate general principles of
pattern formation. I have used iPSC to successfully establish two 3D models recapitulating spatiotemporal
features of human somite formation, which provide a valuable platform to decode mechanisms of body axis
patterning with unprecedented resolution. Using these models, I found that active cell sorting underlies the
antero-posterior (AP) polarity patterning of somites and put forward a novel framework explaining the formation
of repeated structures along the body axis. In this proposal I will further utilize the in vitro models to expand and
refine the cell sorting centered framework of somite AP patterning, as well as develop 3D models of human limb
development to set up foundation for my future investigation of digit periodic patterning.
 In Aim1, I will investigate how cell sorting are coordinated with classical modules of somitogenesis. In the
mentored phase, I will uncover roles of the segmentation clock in synchronizing the onset of cell sorting within a
forming segment to ensure robust tissue-level patterning. In the independent phase, I will interrogate how somite
size control is coordinated with AP pattern formation. Together these will bridge the novel finding of cell sorting
with established concepts of somitogenesis. In Aim2, I will elucidate the molecular and cellular mechanisms of
cell sorting and shine light on general cell biological principles of pattern formation. In parallel, I will set out to
develop organoid models of human limb development using iPSCs. In Aim3, I will combine a preliminary 2D
differentiation protocol of Limb bud cells in the Pourquie lab, the expertise in maintaining limb progenitors in vitro
of the Tabin lab, and my specialty in 3D organoid culture to build 3D models recapitulating features of limb bud
elongation and patterning.
 The proposed work will strengthen my knowledge of body axis development, equip me with expertise in
limb development, and establish groundwork for my future career in elucidating periodic pattern formation during
human development. Altogether, this proposal will provide valuable insights into the early development of human
body plan and guide complex organ engineering to further dissect mechanisms and treat diseases.

## Key facts

- **NIH application ID:** 10800763
- **Project number:** 5K99HD111689-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Yuchuan Miao
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $115,579
- **Award type:** 5
- **Project period:** 2023-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800763

## Citation

> US National Institutes of Health, RePORTER application 10800763, Deconstructing human body plan development with stem cells (5K99HD111689-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10800763. Licensed CC0.

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