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Investigating human cis-regulatory evolution with hybrid iPS cells

Award Number: R01HG012285
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/25/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Investigating human cis-regulatory evolution with hybrid iPS cells - Project Summary Despite a great deal of research, we have discovered surprisingly little about the genetic basis of uniquely human traits—largely due to the ethical and practical considerations that severely limit comparisons between humans and other primates. To advance this field, we have integrated two effective approaches for studying evolution: induced pluripotent stem (iPS) cells, and interspecific hybrids. iPS cells can be differentiated into a wide range of cell types in vitro, circumventing many limitations of primate research, while measurement of allele-specific gene expression in hybrids allows cis-regulatory divergence and gene expression adaptations to be mapped genome-wide. To combine these approaches, we have recently generated human/chimpanzee hybrid iPS cells. We propose to characterize this powerful resource with RNA-seq and cellular phenotyping in diverse cell types, including cardiomyocytes, motor neurons, hepatocytes, pancreatic progenitors, skeletal muscle, retinal pigmented epithelium, and skin organoids that include dermis/epidermis, adipose, cartilage, hair follicles, and more. Our goal is to discover and experimentally validate genes and genetic variants that have contributed to the evolutionary origin of our species.


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 = $689,916 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	000	4	8/1/2025	NON-COMPETING CONTINUATION	$689,916
														Subtotal = $689,916

Issue Date FY: 2024 ( Subtotal = $681,479 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	000	3	3/29/2024	NON-COMPETING CONTINUATION	$625,849
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	001	3	7/30/2024	NON-COMPETING CONTINUATION	$55,630
														Subtotal = $681,479

Issue Date FY: 2023 ( Subtotal = $692,436 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	000	2	3/24/2023	NON-COMPETING CONTINUATION	$692,436
														Subtotal = $692,436

Issue Date FY: 2022 ( Subtotal = $760,624 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	000	1	5/25/2022	NEW	$684,563
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Human Genome Research	001	1	9/16/2022	NEW	$76,061
														Subtotal = $760,624

Grand Total All Awards = $2,824,455

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Investigating human cis-regulatory evolution with hybrid iPS cells

Award Number: R01HG012285

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/25/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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