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Defining the heterogeneity of cell lineages in the inter-follicular epidermis

Award Number: R01AR070157
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: 04/12/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Defining the heterogeneity of cell lineages in the inter-follicular epidermis - Abstract Adult skin interfollicular epidermis (IFE) renewal is currently described by simple models of relatively homogenous basal stem/progenitor cells. However, long-term IFE renewal is likely orchestrated by the physiological demands of a complex tissue architecture comprising multiple levels of heterogeneity. We began to elucidate the cellular and molecular organization of two spatially distinct IFE domains, their physiological relevance, and the relationship between mouse and human skin. We demonstrate that molecular and cellular states of mouse tail basal microdomains (scales and inter-scales) recapitulate human skin IFE spatial organization in rete ridges and inter-ridges. We begin to uncover a physiological relevance for the skin spatial domains: adaptation to differential UV exposure. We identify multiple IFE populations with distinct behavior in clonal analysis and describe the first in vivo epidermal transit-amplifying (TA) cell. The later uniquely displays a maturation-dependent behavior with a timed-transition from an amplification phase to an extinction phase. This opens-up a new road for investigating molecular mechanisms of timed transitions from a ‘young’ to a ‘mature’ cell state. Using mouse genetics, we develop new tools to label and characterize IFE domains that are most UV exposed and examine in depth: (1) IFE spatial heterogeneity and domain organization in skin and its physiological significance; and (2) the heterogeneity of IFE stem/TA population behavior in skin, how this relates to regeneration capacity of spatial domains, and what are the mechanisms of cell fate transition from a young to a mature TA cell state, and from a stem to a TA cell. We propose that the extraordinary IFE complexity of basal cell states, multiple stem/TA cell populations, and spatial organization may explain the unusual robustness of skin homeostasis in response to constant environmental challenges.


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 = $447,043 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	2/19/2025	NON-COMPETING CONTINUATION	$447,043
														Subtotal = $447,043

Issue Date FY: 2024 ( Subtotal = $533,234 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	2/22/2024	NON-COMPETING CONTINUATION	$494,754
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	5/21/2024	NON-COMPETING CONTINUATION	$38,480
														Subtotal = $533,234

Issue Date FY: 2023 ( Subtotal = $559,830 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	4/12/2023	COMPETING CONTINUATION	$559,830
														Subtotal = $559,830

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	9/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $339,563 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	3/26/2021	NON-COMPETING CONTINUATION	$315,058
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	6/7/2021	NON-COMPETING CONTINUATION	$24,505
														Subtotal = $339,563

Issue Date FY: 2020 ( Subtotal = $350,215 )
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/23/2020	NON-COMPETING CONTINUATION	$350,215
														Subtotal = $350,215

Issue Date FY: 2019 ( Subtotal = $350,347 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/15/2019	NON-COMPETING CONTINUATION	$350,347
														Subtotal = $350,347

Issue Date FY: 2018 ( Subtotal = $350,465 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/14/2018	NON-COMPETING CONTINUATION	$350,465
														Subtotal = $350,465

Issue Date FY: 2017 ( Subtotal = $350,570 )
2017	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/9/2017	NEW	$350,570
														Subtotal = $350,570

Grand Total All Awards = $3,281,267

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Defining the heterogeneity of cell lineages in the inter-follicular epidermis

Award Number: R01AR070157

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: 04/12/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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