# Identification and single cell analysis of embryonic lymphoid progenitors that generate neonatal innate T cells

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $496,750

## Abstract

Project Summary
Certain infections during pregnancy are linked to developmental and behavioral abnormalities in
the offspring. Whether overt inflammatory responses in the mother can have a lasting impact on
the development of immune system of the offspring is unknown. This gap in knowledge is directly
linked to a lack of detailed insights into how lymphocytes normally develop in the fetus. How
animals generate multiple immunocyte subtypes from fetal to aged stages remains an active area
of research with many unresolved fundamental questions. In particular, it is unknown whether
the immune system is a) one dimensional, a collective of diverse cell types generated from a single
stem cell or is b) multi-layered, with each layer made of functionally specialized cell systems
tailored to the distinct developmental age of an animal. We discovered that skin lymphocytes
(immune sentinels) essential to prevent dermatitis originate from progenitors with dedicated
gene programs that only develop in embryos. Importantly, data further suggest that the unique
genetic networks of immune sentinels are active in fetal tissues prior to the emergence of a single
hematopoietic stem cell (HSC) in the fetal liver. It has been assumed that fetal HSCs are the
primary stem cell for all lymphocytes. Our results thus suggest the existence of undiscovered
embryonic innate lymphoid progenitors (eILPs) distinct from classical HSCs or their immediate
daughter cells primed toward the lymphoid lineage. We plan to identify and characterize eILP
subtypes by employing a spectrum of molecular beacons, each embedded in the genome and
reporting the activity of predicted gene network hubs of eILPs. Rare cells in the fetus with a
specified combination of beacons will be captured and these candidate eILPs will be analyzed
molecularly at a single cell level and transplanted into animals to determine their generative
potential. Candidate eILPs are predicted to preferentially generate mucosal immune sentinels in
fetal and neonatal animals, and once these sentinels are made they persist long term, well into
adulthood. Absence or alterations of these innate sentinels results in aberrant tissue homeostasis
and inflammatory disorders. Once the embryonic hematopoietic lineage tree is constructed how
immune perturbations in pregnancy impact the development of innate lymphocytes can be
systematically assessed.

## Key facts

- **NIH application ID:** 10159863
- **Project number:** 5R01AI147685-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Joonsoo Kang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $496,750
- **Award type:** 5
- **Project period:** 2019-06-12 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159863

## Citation

> US National Institutes of Health, RePORTER application 10159863, Identification and single cell analysis of embryonic lymphoid progenitors that generate neonatal innate T cells (5R01AI147685-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10159863. Licensed CC0.

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