# Repressing TGFbeta family signaling to promote hematopoietic stem cell formation in the embryo

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $330,170

## Abstract

Summary
The goal of this proposal is to understand how transforming growth factor beta (TGFb) family
signaling regulates the formation of hematopoietic stem cells (HSCs) in the embryo. All HSCs in
the adult bone marrow are descendants of pre-hematopoietic stem cells (pre-HSCs) that
differentiate from hemogenic endothelial (HE) cells in the major caudal arteries of the embryo.
However, only a subset of hematopoietic cells that differentiate from HE cells in the arteries are
pre-HSCs, while many are committed lympho-myeloid biased progenitors. We generated a
comprehensive single cell dataset covering the developmental trajectory of blood cell formation
from HE cells and identified genes specifically expressed in pre-HSCs. We demonstrate that one
of these genes, Smad7, which is a negative regulator of TGFb family signaling, is required for the
formation of multi-lineage adult-repopulating HSCs in the embryo but is not required for the
generation of lympho-myeloid biased progenitors. The goals of this proposal are to determine at
what step of HSC formation or function the restraint of TGFb family signaling by SMAD7 is
required (pre-HSC formation, pre-HSC to HSC maturation, HSC self-renewal), and which TGFb
family signaling pathway SMAD7 restrains to allow HSCs to form in the embryo or function in the
adult.

## Key facts

- **NIH application ID:** 10788436
- **Project number:** 5R01HL163265-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** NANCY SPECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $330,170
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788436

## Citation

> US National Institutes of Health, RePORTER application 10788436, Repressing TGFbeta family signaling to promote hematopoietic stem cell formation in the embryo (5R01HL163265-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10788436. Licensed CC0.

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