Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The role of retinoid exposure in specification of the foundational SSC pool

Award Number: R01HD090083
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/26/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2023

Group Awards By:

View Award Description

The role of retinoid exposure in specification of the foundational SSC pool - PROJECT SUMMARY/ABSTRACT Spermatogenesis begins in the neonatal mouse testis with the segregation of prospermatogonia into distinct undifferentiated and differentiating populations. A proportion of undifferentiated spermatogonia retain stem cell potential (as foundational spermatogonial stem cells, or SSCs), and the remainder becomes progenitor spermatogonia that proliferate and differentiate in response to retinoic acid (RA). This initial fate decision is critical, as imbalances cause spermatogenic defects that can lead to human testicular cancer or infertility. It is currently unknown how spermatogonial fate decisions are regulated. We have recently made the exciting discovery that neonatal male germ cells differ in their responsiveness to RA both in vivo and in vitro (in the absence of the niche environment). As early as postnatal day (P) 1, we can identify two distinct subpopulations of prospermatogonia: 1 – those that cannot respond to RA (‘RA-non-responsive’) either in vitro or in vivo, and 2 – those that can respond but do not yet in vivo (‘RA-responsive’). The objective of this proposal is to determine whether the foundational SSC pool forms from prospermatogonia that are intrinsically preprogrammed (predetermination) or from those that happen to occupy a limited number of stem cell niches (selection). Our data strongly suggest that some prospermatogonia are predetermined to remain undifferentiated and become SSCs, and that this fate is manifest by an inability to respond to the proliferation and differentiation signal provided by RA. In the proposed aims, we will explore whether this RA insensitivity is intrinsic (germ cell autonomous) or determined by somatic cells (germ cell non-autonomous), define when during postnatal development differential RA responsiveness appears, and determine whether the foundational SSC pool is formed solely from these RA-insensitive germ cells. In Aim 1, we will assess gene expression heterogeneity associated with neonatal germ cell RA responsiveness. Heterogeneous expression of genes involving RA responsiveness by either the germline or soma could explain which compartment dictates the fate of SSC precursors. In Aim 2, we will define the roles of RA reception and catabolism in RA responsiveness. We predict that RA insensitivity is intrinsically preprogrammed, long lasting, and defines the foundational SSC population. In Aim 3, we will determine whether RA-insensitive prospermatogonia preferentially give rise to foundational SSCs. We will modulate RA levels in vivo and examine the subsequent effect on formation of the foundational SSC pool. Together, the results of these aims will define how RA responsiveness contributes to formation of the foundational SSC pool in the neonatal testis.


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 = -$10,204 )
2024	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	5	12/5/2023	NON-COMPETING CONTINUATION	-$10,204
														Subtotal = -$10,204

Issue Date FY: 2021 ( Subtotal = $294,345 )
2021	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	001	5	3/25/2021	NON-COMPETING CONTINUATION	$0
2021	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	002	5	3/31/2021	NON-COMPETING CONTINUATION	$0
2021	2021	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	5	2/12/2021	NON-COMPETING CONTINUATION	$294,345
														Subtotal = $294,345

Issue Date FY: 2020 ( Subtotal = $300,505 )
2020	2020	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	4	2/20/2020	NON-COMPETING CONTINUATION	$300,505
														Subtotal = $300,505

Issue Date FY: 2019 ( Subtotal = $300,652 )
2019	2019	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	3	3/4/2019	NON-COMPETING CONTINUATION	$300,652
														Subtotal = $300,652

Issue Date FY: 2018 ( Subtotal = $271,033 )
2018	2018	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	2	2/15/2018	NON-COMPETING CONTINUATION	$243,929
2018	2018	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	001	2	4/19/2018	NON-COMPETING CONTINUATION	$27,104
														Subtotal = $271,033

Issue Date FY: 2017 ( Subtotal = $274,005 )
2017	2017	EAST CAROLINA UNIVERSITY	1000 E 5TH ST	GREENVILLE	NC	27858	PITT	USA	Child Health and Human Development Extramural Research	000	1	3/27/2017	NEW	$274,005
														Subtotal = $274,005

Grand Total All Awards = $1,430,336

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of retinoid exposure in specification of the foundational SSC pool

Award Number: R01HD090083

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/26/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer