# Transcription regulation in hematopoiesis

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $450,207

## Abstract

Project Summary (Project 2)
 Cellular therapy, including hematopoietic stem/progenitor cell (HSPC) transplant, is a critical part of
transfusion medicine practice. Umbilical cord blood can be an excellent alternative HSPC donor source;
however its use is severely constrained by the limited HSPC numbers in one single cord blood unit. Despite
our progress in understanding the molecular factors that support the self-renewal and differentiation of the
hematopoietic system in vivo, less is known on how to modulate the factors that govern the self-renewal of
HSPCs ex vivo. Unlike in the case of embryonic stem (ES) cells, expansion of HSPC in culture in general is at
the expense of “stemness”. We hypothesize that the HSPC fate is governed by key transcription factors, which
are down-regulated during HSPC ex vivo expansion. Transcription factors maintain the HSPC identity by
bookmarking the epigenetic memories during cell division. Identifying these transcription factor(s) is critical for
the development of ex vivo HSPC expansion technology. ES cell gene SALL4 is a zinc finger transcription
factor. It plays vital roles in the maintenance of ES cell properties. SALL4 is also a key factor in regulating
human normal hematopoiesis, and can be used to expand cord blood HSPC population. The mechanism(s) of
SALL4 in normal hematopoiesis, at least in part, is through its transcription activation domain and its interaction
with the MLL epigenetic complex. Based on our preliminary studies, we propose the SALL4 transcription
activation function is important for CD34+ HSPC expansion, and discovery of novel pharmacological tools to
enhance its transcription activation property could potentially lead to new HSPC expansion technology. We
have proposed the following specific aims: Specific Aim I: Characterize the functional role(s) of SALL4
transcription activation domain in HSPC expansion. Specific Aim II: Determine the molecular mechanism of
SALL4 transcription activation domain in HSPC expansion. Specific Aim III: Screen and identify small molecule
compounds to enhance SALL4 mediated HSPC expansion. Our proposed experiments, once completed, not
only can offer us insights on HSPC biology, but also provide us with novel small molecule drugs for the
purpose of HSPC expansion.

## Key facts

- **NIH application ID:** 9897591
- **Project number:** 5P01HL095489-10
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Li Chai
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,207
- **Award type:** 5
- **Project period:** — → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897591

## Citation

> US National Institutes of Health, RePORTER application 9897591, Transcription regulation in hematopoiesis (5P01HL095489-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897591. Licensed CC0.

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