# Characterizing transient hematopoietic multipotent and megakaryocyte progenitor cells during postnatal development

> **NIH NIH F30** · LOYOLA UNIVERSITY CHICAGO · 2022 · $33,330

## Abstract

Abstract
 Fetal hematopoiesis has properties distinct from adult hematopoiesis, explaining the unique features of
infant myeloproliferative disorders and leukemia. Adult-type hematopoietic stem cells (HSCs) are generated in
the major arteries in the aorta-gonad-mesonephros region at embryonic day (E)9.5-E11.5 in mice, colonize the
fetal liver (FL) and fetal bone marrow (BM), and remain in adult BM for an organism’s lifetime. Previous studies
hypothesized that the fetal-to-adult hematopoietic transition is a gradual maturation process of adult type HSCs.
However, two fetal-type hematopoietic progenitors (HPCs) originate from the yolk sac hematopoiesis (E7.5 and
E8.5) that also colonize the FL and fetal BM, overlap with maturing HSCs, and are the primary contributors to
hematopoiesis during fetal development. Increased evidence suggests this transition is a combined process of
declining fetal-type HPCs and maturation of adult-type HSCs. However, the cellular and molecular mechanisms
regulating the hematopoietic transition are still largely unknown.
 Green fluorescent protein (GFP) expression in Ctnnal1-GFP reporter mice was shown to specifically label
HSCs in young adults, but not downstream multipotent progenitors (MPPs) or megakaryocyte progenitors
(MkPs). In addition to HSCs in neonatal mice, I found GFP labels a subset of MPP1, MPP2 and MkPs. These
GFP+ HPCs gradually decline until absent by week 4 post-birth, while GFP- MPP1, MPP2, and MkPs remain. As
adult HSC maturation occurs during this period, GFP+ subsets represent novel developmentally restricted HPCs
with unknown origin, function, and regulatory mechanisms. In vitro study demonstrates that GFP+ MPP1, MPP2
and MkPs are distinct from their GFP- counterparts and display many properties of fetal type HPCs. For example,
although both GFP+ and GFP- MPP2s differentiate to monocytes, granulocytes and megakaryocytes (Mk), GFP+
MPP2s are biased to monocyte and Mk differentiation like fetal HPCs, while GFP- MPP2s are biased to
granulocytic differentiation. Compared to Mks produced by GFP- MkPs, GFP+ MkPs produce smaller, lower
ploidy Mks similar to Mks found in fetal BM. I hypothesize that Ctnnal1-GFP+ MPP1, MPP2, and MkPs are
phenotypically and functionally distinct from their Ctnnal1-GFP- counterparts, are derived from fetal type HPCs
independent of adult HSCs, and represent novel transient populations that are capable of initiating infant
hematological diseases. I intend to address this hypothesis by (1) fully characterizing the biology and function of
GFP+ MPP1, MPP2, and MkPs; and (2) determining where they arise and if they are derived from fetal type
HPCs independent of adult HSCs. To do so, I will use three mouse models: Ctnna1-GFP mice for in vitro and
flow cytometry experiments, Ctnna1-GFP/Rosa26-tdTomato mice for transplantations, and Cdh5Cre-Ert/Ctnnal1-
GFP/Rosa26-tdTomato mice to determine the origin of GFP+ cells. Success of this study will not only help to
understand the mechanism...

## Key facts

- **NIH application ID:** 10537794
- **Project number:** 1F30HL162475-01A1
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Ryan Mack
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $33,330
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537794

## Citation

> US National Institutes of Health, RePORTER application 10537794, Characterizing transient hematopoietic multipotent and megakaryocyte progenitor cells during postnatal development (1F30HL162475-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10537794. Licensed CC0.

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