# Stem Cell-Niche Interactions in the Establishment of Hematopoietic Stem Cell Heterogeneity

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $33,227

## Abstract

ABSTRACT
 Within the blood there is abundant diversity among hematopoietic stem cells (HSCs) in lineage
contribution, proliferation, stimuli response, and surface markers. While HSC heterogeneity has been observed
during embryonic development, it is unclear how it is generated. My goal is to understand how clonal diversity
in HSCs is specified. Hematopoietic stem and progenitor cells (HSPCs) form from budding endothelial cells in
the aorta-gonad-mesonephros (AGM), and temporarily colonize the fetal liver in mammals or the caudal
hematopoietic tissue (CHT) in zebrafish, before homing to the adult niche in bone or kidney marrow,
respectively. HSC subtype behaviors can be found as early as fetal-liver stage and are remarkably stable, with
lineage-biases maintained even after serial transplantation. This is suggestive of a model in which early events
in development establish intrinsic clonal behavior in HSCs that persists throughout the life of the animal. I
hypothesize that signals in the AGM and CHT establish long-lasting clonal differences in emerging and
nascent HSCs. This project aims to define the role of embryonic microenvironments in establishing HSC clonal
lineage skews and to investigate candidate cellular and genetic effectors of HSC clonal behavior. To
accomplish this, I have established a novel method for rapid enrichment of rare embryonic cells, a technical
hurdle that has previously hindered efforts to measure these rare developmental events in a high-throughput
manner. Experiments outlined in Aim 1 will 1) identify transcriptional diversity in nascent HSPCs to determine
when subtypes are established in stem cell induction and 2) test candidate pathways implicated in establishing
HSC subtypes. Aim 2 will specifically interrogate the role of primitive macrophages in regulating the nascent
HSC pool by identifying and perturbing molecular changes induced after cell-cell interactions in the CHT.

## Key facts

- **NIH application ID:** 10001335
- **Project number:** 5F31HL149154-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Samuel Wattrus
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,227
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001335

## Citation

> US National Institutes of Health, RePORTER application 10001335, Stem Cell-Niche Interactions in the Establishment of Hematopoietic Stem Cell Heterogeneity (5F31HL149154-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001335. Licensed CC0.

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