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Clarifying the Origins of Blood Stem Cell Heterogeneity by Single-Cell Epigenetic State Profiling

Award Number: R56DK132084
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: 09/23/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Clarifying the Origins of Blood Stem Cell Heterogeneity by Single-Cell Epigenetic State Profiling - Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Evaluating the extent and dynamics of epigenetic heterogeneity in blood stem cells at the single-cell level Proper control of hematopoietic stem cell (HSC) self-renewal and differentiation is essential for all humans, not only during healthy conditions, but also for the treatment of various hematological disorders through bone marrow transplantations. Understanding the mechanisms of hematopoiesis is therefore vital for understanding healthy physiology and for creating efficient and rational approaches for blood cell regeneration therapies. Intriguingly, prior research has reported substantial heterogeneity in the distributions of final cell fates for the descendants of individual HSCs, even for clonally related cells in identical environments. These differences in lineage potential could result from differences in epigenetic state, however, the study of epigenetic states at the level of individual stem cells has been hindered by limitations in available methodology. To overcome these limitations, we have developed a new microscopy-based assay called SCEPTRE (Single-Cell Evaluation of Post-TRanslational Epigenetic encoding) that can sensitively resolve epigenetic states at single gene loci in single cells (Woodworth et al. 2021). In Aim 1 we will use SCEPTRE to study histone post-translational modifications in HSCs at key gene loci governing lymphomyeloid differentiation. In Aim 2, toward the goal of analyzing epigenetic state dynamics, we will develop a live imaging assay for tracking HSC clones over multiple cell generations that we will then combine with SCEPTRE to probe epigenetic heritance at the clonal level. If successful, this work will open the door for future studies that clarify the origins and consequences of heterogeneity in HSC biology.


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	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $77,535 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/22/2023	NON-COMPETING CONTINUATION	$77,535
2023	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/21/2023	NEW	$0
														Subtotal = $77,535

Issue Date FY: 2022 ( Subtotal = $99,374 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/22/2022	NEW	$99,374
														Subtotal = $99,374

Grand Total All Awards = $176,909

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Clarifying the Origins of Blood Stem Cell Heterogeneity by Single-Cell Epigenetic State Profiling

Award Number: R56DK132084

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: 09/23/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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