# Identification of novel regulators of HSC specification and maturation

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $286,464

## Abstract

Identification of novel regulators of HSC specification and maturation
Project Abstract
Hematopoietic stem cells (HSCs) are defined by self-renewal and multilineage differentiation capacities. HSCs
sustain lifelong hematopoiesis and are exploited for hematopoietic transplantation to replace damaged or
diseased blood systems in patients with hematologic disorders. Despite the widespread usage, transplantation
remains unattainable for many due to the paucity of appropriate immunologically matched donors. De novo
production of HSCs from patient-specific induced pluripotent stem cells (iPSCs) has been proposed as a means
to circumvent this problem, but it remains an extremely inefficient process. Current approaches result in the
abundant creation of hematopoietic progenitors that possess limited differentiation abilities and lack sufficient
transplantation capacity. During development, there is simultaneous de novo production of these limited-capacity
progenitors alongside HSCs. One of the major limitations in the field is the inability to distinguish these cells at
the time of formation, which makes it difficult to define the factors distinctly critical for HSC generation. Through
single-cell RNA-sequencing of nascent hematopoietic stem and progenitor cells from developing zebrafish, we
identified genes that discriminate HSCs from progenitors at the time of their formation. We also developed new
in situ lineage-tracing and regenerative assays in zebrafish larvae to define functional differences between the
differentiation kinetics and self-renewal of these cell subsets. Here, we plan to exploit the genetic malleability of
zebrafish coupled with our novel assays to discover new regulators uniquely required for HSC formation. The
SHINE-II mechanism (PAS-18-730) is dedicated to supporting new research directions in their early stages.
Consistent with this aim, this project takes our laboratory in a new direction away from our focus on RNA
processing in hematopoiesis and into the realm of understanding de novo production of bona fide HSCs. Our
experience in zebrafish genetics and developmental biology along with our establishment of new assays to
functionally distinguish nascent HSCs from HSC-independent progenitors make us well-positioned to accomplish
our goal of identifying novel factors that uniquely regulate HSC specification and functional maturation.
Identifying this program will provide fundamental knowledge on the acquisition of self-renewal and multipotency
attributes and could provide guidance to improve ex vivo HSC production from mammalian iPSCs.

## Key facts

- **NIH application ID:** 10356477
- **Project number:** 1R01DK131445-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Teresa V Bowman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $286,464
- **Award type:** 1
- **Project period:** 2021-09-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356477

## Citation

> US National Institutes of Health, RePORTER application 10356477, Identification of novel regulators of HSC specification and maturation (1R01DK131445-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356477. Licensed CC0.

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