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A generalizable framework for linking single-cell genomic states with cell fate outcomes in hematopoiesis

Award Number: RC2DK122376
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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A generalizable framework for linking single-cell genomic states with cell fate outcomes in hematopoiesis - PROJECT SUMMARY Currently, conventional methods that have been utilized to characterize hematopoietic progenitors and their potentials including flow cytometry, in vitro colony-forming-unit assays and in vivo genetic marking are being vigorously complemented with genomics analyses such as single-cell RNA-Seq (scRNA-Seq) and scATACSeq. While these complementary analyses are defining a multitude of possible cell states, there is considerable confusion concerning the correspondence between such states and the heterogeneity/identity of cells captured within canonical flow cytometry gates, their developmental potentials, and mechanisms underlying lineage specification. To address this fundamental problem in the field we have assembled an interdisciplinary research team with deep expertise in the application of single-cell technologies, hematopoiesis, computational genomics and systems biology to develop and promote a unifying framework for the analysis of genomic states with their developmental potentials and trajectories. Specifically, we will define prevalent and rare hematopoietic intermediates as well as their developmental potencies, restrictions and trajectories, on the basis of their genomic states along with the optimal markers and flow gates necessary to isolate them. Using these genomic datasets coupled with analyses of poised or active enhancers interacting with promoters, we will infer gene regulatory networks (GRNs) that delineate the connectivity of transcription factors to their target genes thereby inferring control mechanisms underlying the distinctive genomic states. Thus, exploiting a consolidated biological, molecular and computational dissection of the hematopoietic system focusing on underlying genomic regulatory architectures, we will provide a new framework to incisively understand steady state hematopoiesis.


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 = $0 )
2026	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	1/2/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,019,079 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/11/2024	NON-COMPETING CONTINUATION	$1,019,079
														Subtotal = $1,019,079

Issue Date FY: 2023 ( Subtotal = $1,061,539 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/30/2023	NON-COMPETING CONTINUATION	$1,061,539
														Subtotal = $1,061,539

Issue Date FY: 2022 ( Subtotal = $1,061,539 )
2022	2022	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/13/2022	NON-COMPETING CONTINUATION	$1,061,539
														Subtotal = $1,061,539

Issue Date FY: 2021 ( Subtotal = $1,061,539 )
2021	2021	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/24/2021	NON-COMPETING CONTINUATION	$1,061,539
														Subtotal = $1,061,539

Issue Date FY: 2020 ( Subtotal = $1,061,540 )
2020	2020	CHILDREN'S HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/13/2020	NEW	$1,061,540
														Subtotal = $1,061,540

Grand Total All Awards = $5,265,236

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A generalizable framework for linking single-cell genomic states with cell fate outcomes in hematopoiesis

Award Number: RC2DK122376

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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