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Investigating the hydraulic regulation of human gastrulation and mesodermal patterning using stem cells

Award Number: K99HD120644
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Investigating the hydraulic regulation of human gastrulation and mesodermal patterning using stem cells - Investigating the Hydraulic Regulation of Human Gastrulation and Mesodermal Patterning Using Stem Cells Abstract Human embryonic development is orchestrated by complex biochemical and mechanical cues that guide cellular differentiation and tissue patterning. This proposal seeks to investigate the role of mechanics in regulating mesoderm induction and patterning during gastrulation, a critical event that establishes body axes and forms the foundation of all tissues. These early stages are highly sensitive, with up to 50% of pregnancies failing due to developmental errors within the first few weeks. Despite advances in understanding the genetic regulation of mesodermal fate, the roles of amniotic cavity pressure and epiblast shape in mesoderm induction and patterning remain poorly understood due to ethical and technical limitations in studying human embryos. Using a novel three-dimensional stem cell-based model, termed “Lumenoids,” this study aims to dissect the mechanobiological principles underlying early embryogenesis. The proposed research is structured into three key aims: (1) to elucidate how fluid pressure in the amniotic cavity, cortical tension, and geometric constraints influence mesoderm induction; (2) to identify how pressure influences signaling in the mesodermal gene regulatory network; and (3) to explore mechanotransduction pathway and the role of extra-embryonic tissue, hypoblast in shaping mesodermal patterning. By integrating biophysical measurements, live imaging, spatial transcriptomics, and genetic perturbations, this study will systematically investigate the impact of mechanical forces on cell fate decisions. Findings from this research have significant implications for regenerative medicine, improving strategies for directed differentiation of stem cells, and providing insights into early pregnancy loss. By uncovering fundamental mechanobiological processes that regulate early human development, this study will contribute to our understanding of embryogenesis, reproductive health, and stem cell biology.


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: 2026 ( Subtotal = $128,331 )
2026	2026	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	8/21/2026	NEW	$128,331
														Subtotal = $128,331

Grand Total All Awards = $128,331

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Investigating the hydraulic regulation of human gastrulation and mesodermal patterning using stem cells

Award Number: K99HD120644

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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