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Role of interdigitating secretory cells in regulation of intestinal stem cells during development

Award Number: R15HD088202
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary/Abstract While the structure of the adult intestinal stem cell niche has become well defined, little is know about the structure and regulation of the immature stem cell niche. In the adult mammalian crypt, dedicated stem cells are referred to as Crypt Base Columnar (CBC) cells are regulated by interdigitated Paneth cells in the small intestine and a subtype of goblet cells in the large intestine. Here we propose that the immature stem cell compartment is regulated by cells analogous to the Paneth and goblet cells, that regulate growth and transformation of an immature stem cell niche into the adult structure. Using the advantages of external development and transparency of the zebrafish model system to manipulate and visualize the developing intestine, we identify regulatory cells within the immature stem cell compartment, which differentiate at the fold base beginning at the end of embryogenesis and continuing through juvenile phase. Preliminary data indicates that these cells are involved negative regulation of epithelial proliferation and there are two different groups, one group that differentiates during the first half of juvenile period and a second group that forms as the intestine matures to the adult structure. In Aim 1 we will focus on disrupting the function of these cells to determine their role in regulation of the architecture of the developing stem cell compartment leading up to maturation of the adult intestinal stem cell compartment. In Aim 2 we will determine whether the identified regulatory cells modulate epithelial proliferation by modulating the Wnt pathway. Finally, in Aim 3, we will determine whether thyroid hormone plays a role in differentiation of the group of regulatory cells that differentiates as the intestine matures to the adult structure. Together, these studies will identify new features of the network controlling growth of the immature stem cell compartment as it matures into the adult structure. In the long term, this work has the potential to shed light on intestinal diseases resulting from congenital defects due to errors during establishment of the intestinal epithelial stem cell compartment.


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: 2023 ( Subtotal = $0 )
2023	2017	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Child Health and Human Development Extramural Research	000	1	10/1/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2017	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Child Health and Human Development Extramural Research	000	1	6/25/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $423,920 )
2017	2017	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Child Health and Human Development Extramural Research	000	1	8/6/2017	NEW	$423,920
														Subtotal = $423,920

Grand Total All Awards = $423,920

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Role of interdigitating secretory cells in regulation of intestinal stem cells during development

Award Number: R15HD088202

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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