# Mapping human hematopoietic stem cell development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $312,000

## Abstract

SUMMARY
Pluripotent stem cells (PSC) are an ideal source for deriving HLA-matched or patient specific hematopoietic stem
cells (HSC) for the treatment of blood disorders. However, all the efforts in producing self-renewing
hematopoietic stem cells (HSC) from PSC have failed due to our limited understanding of the mechanisms that
govern “stemness” in developing human HSC. Although the transcription factors that drive blood specification
are relatively well understood, we lack knowledge of the programs that define HSC self-renewal, and why these
programs fail in PSC derived hematopoietic cells. Thus, we aim to create a single cell transcriptome map of
human HSC ontogeny in vivo and ESC derived cells generated in vitro. The ability to compare human HSC from
the critical stages of ontogeny when HSCs are specified (AGM, and possibly the placenta and yolk sac) and
expand and mature into fully functional HSC in the conceptus (fetal liver and fetal bone marrow) will allow us to
identify pathways that are critical for HSC self-renewal, and that distinguish human HSCs developing in vivo from
those that develop in vitro. This analysis will pinpoint key defects that underlie the poor function of ESC derived
hematopoietic cells, and offer new solutions for overcoming these molecular barriers. As there is a lack of HSC
surface markers that would reliably predict human HSC function, to help monitor the differentiation of properly
specified HSCs, we created hESC reporter lines for critical HSC regulatory factors HOXA5, MLLT5 and HLF
whose expression is highly enriched in self-renewing human HSCs. We will then compare the in vitro derived
candidate HSC to the single cell hemato-vascular lineage map of human hematopoietic tissues as HSCs emerge
and expand in vivo. This SHINE-II RO1 is designed to address critical hurdle steps in in vitro HSC generation.
These studies can be expanded to mechanistic studies to understand human HSC regulation, and ultimately to
translational studies to improve HSC transplantation.

## Key facts

- **NIH application ID:** 9998658
- **Project number:** 1R01DK125097-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hanna Katri Annikki Mikkola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $312,000
- **Award type:** 1
- **Project period:** 2021-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998658

## Citation

> US National Institutes of Health, RePORTER application 9998658, Mapping human hematopoietic stem cell development (1R01DK125097-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9998658. Licensed CC0.

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