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Mechanisms Controlling Cellular Differentiation and Proliferation in a Plant Stem Cell Microenvironment

Award Number: R15GM114733
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2015
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Mechanisms Controlling Cellular Differentiation and Proliferation in a Plant Stem Cell Microenvironment - Project Summary/Abstract The development of multicellular organisms is driven by the activity of stem cell populations. Stem cells reside in microenvironments or “niches” that carefully balance the processes of cell self-renewal and differentiation. Disruptions in this balance can lead to severe developmental abnormalities, including congenital defects and cancer. Uncovering the processes regulating stem cell behavior will lead to more effective treatments and cures for such conditions. Our long-term objectives include identifying and characterizing the factors involved in maintaining the stem cell niche and controlling stem cell proliferation. To achieve these goals, we will take advantage of the easily accessible stem cell populations of the model plant Arabidopsis thaliana. Our first specific aim is to characterize key transcriptional regulators that maintain stem cell function by repressing differentiation-promoting genes. We have identified the Arabidopsis histone deacetylase HDA19, corepressor TPL, and transcription factor FD as key repressors of fate-specifying genes in multiple stem cell niches. These include the reproductive shoot apical meristem, responsible for reiteratively initiating flowers, and the floral meristem, which produces individual floral organs. We will identify and functionally characterize protein interactors that form complexes with these three transcriptional regulators to control gene expression in meristems, thereby revealing novel mechanisms underlying stem cell maintenance. In our second aim, we will investigate how reproductive output and age promote the arrest of stem cell activity. Using multiple transcriptomic and high-throughput protein interaction approaches, we have generated a promising list of transcription factors that control stem cell quiescence in response to seed production or age. Notably, related subfamilies of transcription factors appear to modulate meristem function in response to both these developmental variables. We will determine the precise roles of these factors in the promotion of stem cell quiescence through genetic, molecular and biochemical analyses. Moreover, by manipulating the expression of these quiescence-associated genes, we expect to controllably alter the duration of the plant reproductive stage. Collectively, our approaches will characterize the protein factors and molecular mechanisms that modulate stem cell proliferation and niche maintenance in multicellular eukaryotes.


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: 2024 ( Subtotal = -$10 )
2024	2019	AMERICAN UNIVERSITY	4400 MASSACHUSETTS AVE NW	WASHINGTON	DC	20016	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	000	2	1/8/2024	COMPETING CONTINUATION	-$10
														Subtotal = -$10

Issue Date FY: 2019 ( Subtotal = $390,993 )
2019	2019	AMERICAN UNIVERSITY	4400 MASSACHUSETTS AVE, NW	WASHINGTON	DC	20016	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	000	2	9/16/2019	COMPETING CONTINUATION	$390,993
2019	2019	AMERICAN UNIVERSITY	4400 MASSACHUSETTS AVE, NW	WASHINGTON	DC	20016	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	002	2	9/23/2019	COMPETING CONTINUATION	$8
2019	2015	AMERICAN UNIVERSITY	4400 MASSACHUSETTS AVE, NW	WASHINGTON	DC	20016	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	001	1	9/23/2019	NEW	-$8
														Subtotal = $390,993

Issue Date FY: 2015 ( Subtotal = $350,820 )
2015	2015	AMERICAN UNIVERSITY	4400 MASSACHUSETTS AVENUE, NW	WASHINGTON	DC	20016	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	000	1	4/7/2015	NEW	$350,820
														Subtotal = $350,820

Grand Total All Awards = $741,803

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Mechanisms Controlling Cellular Differentiation and Proliferation in a Plant Stem Cell Microenvironment

Award Number: R15GM114733

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2015

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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