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Transcriptional regulation of skin stem cells and their niche

Award Number: R01AR071435
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/28/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Transcriptional regulation of skin stem cells and their niche - Project Summary: The overarching goal of the proposed research is to understand the mechanism of hair follicle stem cell (HF-SC) maintenance and aging. HF-SCs reside in an anatomically distinct region, called the bulge. During the lifespan, HF-SCs go through a multi-stage process, called the hair cycle, to generate hair shaft and self-renew. During the anagen phase of hair cycle, HF- SCs and their hair germ progenitors give rise to a large number of transit-amplifying cells in the Matrix of hair bulb, where precursors to terminally differentiated hair shaft are produced, to fuel hair growth. During the catagen phase, most cells in the lower portion of hair follicles, including the Matrix, undergo apoptosis but a few cells survive and move upward to help to form the new bulge compartment. Upon the formation of the new bulge compartment, HF-SCs usually rest in the quiescent telogen phase before initiating the next anagen hair growth. Although many studies have examined mechanisms that regulate self-renewal and differentiation of HF-SCs, it remains poorly understood how these stem cells quantitatively control hair growth and how their functions decline during aging. In the first funding cycle, we have established skin specific, Foxc1 and Nfatc1 double knockout as a premature aging model for HFs and revealed the escape of HF-SCs from their bulge niche as a new mechanism for the reduction of HF-SCs and HF miniaturization. In our preliminary study, we have generated a hair cycle stage-specific single-cell atlas and a longitudinal single-cell atlas during aging. These rich single-cell transcriptomic datasets have identified a unique cell population of migratory niche (migNiche). Using intravital live imaging to track the duration of hair growth for individual HFs across multiple hair cycles in our mutant model, we have obtained experimental evidence that the size of HF- SC bulge controls the duration of anagen hair growth and the size of HFs and, in turn, define the size of the next-generation bulge. In this proposal, we will utilize our innovative intravital imaging, single-cell genomic tools and genetically engineered mouse models to understand cell extrinsic and cell intrinsic mechanisms of hair follicle stem cell maintenance. We will Investigate the formation of new HF-SC compartment and its effect on hair growth (Aim 1). We will then elucidate FOXC1/NFATC1-mediated gene expression control in the migratory niche (Aim 2). Finally, we will elucidate the mechanism and consequence of HF-SC escape (Aim 3). Together, our renewal application will provide conceptual and mechanistic insights into the maintenance of HF-SCs through a cell extrinsic mechanism mediated by migNiche and a cell intrinsic mechanism controlled by HF-SC adhesion.


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 = $500,821 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	2/14/2025	NON-COMPETING CONTINUATION	$500,821
														Subtotal = $500,821

Issue Date FY: 2024 ( Subtotal = $539,773 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	8	3/19/2024	NON-COMPETING CONTINUATION	$500,821
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	8	6/26/2024	NON-COMPETING CONTINUATION	$38,952
2024	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	3/18/2024	COMPETING CONTINUATION	$15,639
2024	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	3/18/2024	NON-COMPETING CONTINUATION	-$15,639
														Subtotal = $539,773

Issue Date FY: 2023 ( Subtotal = $564,043 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	4/26/2023	COMPETING CONTINUATION	$564,043
2023	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	4/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $564,043

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	7/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $340,586 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	6	6/11/2021	NON-COMPETING CONTINUATION	$341,440
2021	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	4/29/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$33,786
2021	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	5/26/2021	NON-COMPETING CONTINUATION	$0
2021	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/29/2021	NON-COMPETING CONTINUATION	$32,932
														Subtotal = $340,586

Issue Date FY: 2020 ( Subtotal = $322,940 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	9/4/2020	NON-COMPETING CONTINUATION	-$247,567
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	5	9/11/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$237,502
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	7/21/2020	NON-COMPETING CONTINUATION	$333,005
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	9/8/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $322,940

Issue Date FY: 2019 ( Subtotal = $333,173 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	6/6/2019	NON-COMPETING CONTINUATION	$333,173
														Subtotal = $333,173

Issue Date FY: 2018 ( Subtotal = $333,337 )
2018	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/12/2018	NON-COMPETING CONTINUATION	$333,337
														Subtotal = $333,337

Issue Date FY: 2017 ( Subtotal = $314,488 )
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/26/2017	NEW	$314,488
														Subtotal = $314,488

Grand Total All Awards = $3,249,161

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Transcriptional regulation of skin stem cells and their niche

Award Number: R01AR071435

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/28/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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