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The reninness score: integrative analysis of multi-omic data to define renin cell identity

Award Number: F31DK139601
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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The reninness score: integrative analysis of multi-omic data to define renin cell identity - ABSTRACT Renin cells are crucial for survival. They are well-known for their function in blood pressure regulation, fluid- electrolyte homeostasis, kidney development, and tissue morphogenesis. In the fetal kidney, renin cells are progenitors for multiple cell types that retain epigenetic memory of the renin phenotype in adults. When homeostatic threats arise, the descendants of renin progenitor cells can transform to re-express the renin phenotype to restore homeostasis. But the mechanisms of this process, known as recruitment, have yet to be discovered. Furthermore, the regulatory networks that control the identity, fate, and recruitment of renin- expressing cells are unknown. This work comprehensively explores the open chromatin landscape of renin- expressing cells, defines the regulatory factors and transcription factor networks that determine renin cell identity and govern the recruitment process, and develops a novel computational method to score reninness based on epigenetic signals. The rarity of renin cells and the complexity of this phenotype-switching process presents a challenge of distinguishing renin-expressing cells from other kidney cells. This work will address this challenge by integrating ATAC-seq data and RNA-seq data from renin-expressing cells and a wide variety of other cell types. This proposal offers an extensive perspective of the epigenetic landscape of renin-expressing cells and regulatory element changes in the renin recruitment by performing analyses of differentially accessible genomic regions with computational approaches. In addition, it proposes a method to score samples along a spectrum of reninness with given ATAC-seq data. The outcome will aid in overcoming the challenge to identify the rare renin- expressing cells among other kidney cells. This proposal also uses computational approaches to define the transcription factor networks that governs renin recruitment which provides opportunities for follow-up research to verify and potentially fill the gap in understanding the cell-fate switching process mechanisms. Newly defining open chromatin regions and transcription factor networks will improve the scientific understanding of the epigenetic landscape of renin-expressing cells and the mechanisms controlling the identity, fate, and recruitment of renin cells. This proposal has the potential to uncover potential therapeutic targets for alternative treatment for kidney diseases, vascular diseases, and hypertension. The proposed novel computational method to score the reninness from ATAC-seq data will be useful in identifying renin cells in signal-cell data, measuring the level of response of kidney cells under homeostatic threats, predicting renin-related disease progression, and evaluating the effectiveness of treatment for the renin-related disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $41,336 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	3/26/2026	NON-COMPETING CONTINUATION	$576
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/9/2025	NON-COMPETING CONTINUATION	$40,760
														Subtotal = $41,336

Issue Date FY: 2025 ( Subtotal = $40,760 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/3/2024	NEW	$40,196
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	12/3/2024	NEW	$0
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	9/19/2025	NEW	$564
														Subtotal = $40,760

Grand Total All Awards = $82,096

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The reninness score: integrative analysis of multi-omic data to define renin cell identity

Award Number: F31DK139601

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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