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Generation of a temporal, spatial, and molecular map of in situ hematopoiesis

Award Number: RC2DK131963
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: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Generation of a temporal, spatial, and molecular map of in situ hematopoiesis - (PLEASE KEEP IN WORD, DO NOT PDF) Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. The hematopoietic system has been, arguably, the best well studied tissue from a developmental and stem cell biology perspective. Historically, the study of hematopoiesis has taken advantage of flow cytometry and cell transplantation approaches as the gold standard assays to examine functional behaviors. While these studies have provided an elegant textbook view of hematopoiesis, we argue here that our knowledge of how early blood formation works is largely incomplete. This is predominantly due to the limitations of utilizing traditional assays and readouts that disrupt the normal marrow tissue archicture and neglect the anatomical localization of cells. Thus, one key biological component missing in many studies in the field is that of spatial organization. Basic questions such as when and where hematopoietic fate commitment occurs, what the exact cellular intermediates are between a stem cell and mature daughter cells, and what the identity and role of the cellular microenvironement (niche) is in the hematopoietic process remain largely unsettled. Here, we propose an interdisciplinary approach based on state-of-the-art live microscopy manipulations in combination with novel hematopoietic fate reporters to enable a comprehensive study of hematopoiesis entirely in situ. Using novel two photon-guided collection of stem cell clones directly from the bone marrow, and longitudinal live-imaging analysis of stem cell progenies, we aim to generate a spatial, temporal and molecular map of hematopoiesis at single cell resolution. Complementary proximity-based photolabelling approaches will be taken to catalogue the cellular composition of the niche in the steady-sate, diseased, and aged settings. By moving away from tissue disruptive approaches to a system that relies on observation, manipulation, and analysis of single hematopoietic cells within the bone marrow, we hope to obtain unique insights into the cellular organization of blood production.


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: 2025 ( Subtotal = $964,223 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/27/2025	NON-COMPETING CONTINUATION	$964,223
														Subtotal = $964,223

Issue Date FY: 2024 ( Subtotal = $931,458 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/18/2024	NON-COMPETING CONTINUATION	$931,458
														Subtotal = $931,458

Issue Date FY: 2023 ( Subtotal = $974,655 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/30/2023	NON-COMPETING CONTINUATION	$974,655
2023	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/26/2023	NEW	$0
														Subtotal = $974,655

Issue Date FY: 2022 ( Subtotal = $1,000,000 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/1/2022	NEW	$1,000,000
														Subtotal = $1,000,000

Grand Total All Awards = $3,870,336

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Generation of a temporal, spatial, and molecular map of in situ hematopoiesis

Award Number: RC2DK131963

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: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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