New & Noteworthy Publications

The CVG is committed to increasing awareness of current genomics research in our community. Listed below are the latest noteworthy publications from CVG member labs. We hope this will be a helpful way to stay informed of the exciting genomics work that is happening on our campus.

Director's Highlights Spring 2021

Cell Reports Volume 37 Issue 6

MicroRNA-29 specifies age-related differences in the CD8+ T cell immune response.

Mon KJ, Zhu H, Daly CW, Vu LT, Smith NL, Patel R, Topham DJ, Scheible K, Jambo K, Le MT, Rudd BD, Grimson A.
Cell reports. 2021 Nov 9;37(6):109969.

In this inter-disciplinary study across the Grimson and Rudd labs in MBG and M&I, including several other collaborators, the authors show that a specific microRNA family, miR-29, is required for the normal memory response of adult CD8+ T cells. Moreover, gain of miR-29 expression in neonatal cells, which normally exhibit reduced memory response, is sufficient to improve memory response. In addition to the discovery of miR-29 as a master developmental switch, this study raises the possibility that miRNAs could be used as biomarkers of infection outcome and/or vaccine efficacy. Norah Smith, a co-author on this paper, recently received a 2021 CVG seed grant with co-PIs Grimson and Rudd.

Norah Smith
Brian Rudd
Andrew Grimson

Nature Communications

The genetic architecture of DNA replication timing in human pluripotent stem cells.

Ding Q, Edwards MM, Wang N, Zhu X, Bracci AN, Hulke ML, Hu Y, Tong Y, Hsiao J, Charvet CJ, Ghosh S., Handsaker RE, Eggan K, Merkle FT, Gerhardt J, Egli D, Clark AG, Koren A.
Nature Communications. 2021 Nov 19;12(1):1-8

Andy Ding is lead author on a major paper from Amnon Koren’s lab, characterizing both genetic variants and epigenetic signatures designating origins of replication in humans. The work made use of read-depth from whole-genome shotgun sequencing to infer locations of replication origins in dividing cultured pluripotent stem cells from 349 individuals. While the replication origins are largely conserved, more than 1600 DNA sequence variants were associated with inter-individual differences in origin use. A combinatorial epigenetic code was found to be highly predictive of origin use. Listed as co-authors are Matt Edwards (2021 CVG Distiguished Scholar) and Alexa Bracci (2018 CVG Scholar).

Andy Ding
Matt Edwards
Alexa Bracci
Amnon Koren

Biology Open Volume 10 Issue 10

Efficient induction and sustenance of pluripotent stem cells from bovine somatic cells.

Pillai VV, Koganti PP, Kei TG, Gurung S, Butler WR, Selvaraj V.
Biology open. 2021 Oct 15;10(10):bio058756.

In this recent publication, Viju Vijayan Pillai, Prasanthi Koganti and colleagues in the Selvaraj lab used systems biology to identify species-specific pathways associated with pluripotency in cattle. This study was initially funded by a 2011 CVG seed grant, then funded by the USDA in 2013. Iridescent dome-shaped colonies with individual cells not being discernible is a morphological hallmark of naïve pluripotency. This work uncovers core elements of pluripotency signaling in bovids, highlighting species-distinctions that have baffled scientists for decades. The first authors were also featured in this interview.

Vimal Selvaraj

Journal of Nutrition volume 151 Issue 10

Reduced Shmt2 expression impairs mitochondrial folate accumulation and respiration, and leads to uracil accumulation in mouse mitochondrial DNA.

Fiddler JL, Xiu Y, Blum JE, Lamarre SG, Phinney WN, Stabler SP, Brosnan ME, Brosnan JT, Thalacker-Mercer AE, Field MS.
The Journal of Nutrition. October 2021. Volume 151, Issue 10 (p882–2893)

In this study, led by the Field lab in the Division of Nutritional Sciences, the authors use CRISPR/Cas9 technology to study the role of Shmt2 in mitochondrial function and the maintenance of mitochondrial DNA (mtDNA) integrity. A key finding is that while the effects of reduced expression of Shmt2 is, expectedly, more subtle than the effects of a knockout, it can still lead to compromised cellular respiration and proliferation. The authors unveil the mechanistic underpinnings for this observation that opens new areas of research in mitochondrial genome maintenance.

Martha Field

Nature Communications

Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.

Singh, P., Fragoza, R, Blengini, C., Tran, T., Pannafino, G., Al-Sweel, N., Schimenti, K., Schindler, K., Alani, E., Yu, H., and Schimenti, J.
(2021)Nature Comm, 12:5005. PMC8373927

In this study, led by the Yu and Schimenti labs in CB and BMS, the authors used a wide range of approaches, including but not limited to computational predictions, genome editing, and yeast two-hybrid assays, to identify several genetic variants of MLH1 and MLH3 (previously of unknown significance) that cause reproductive defects in mice. The findings of this study have important implications for the mechanisms that underpin early miscarriages in humans.

Haiyuan Yu
John Schimenti

eLife scientific publishing, logo

Planarian stem cells sense the identity of the missing pharynx to launch its targeted regeneration.

Bohr TE, Shiroor DA, Adler CE.
eLife. 2021 Jun 22;10:e68830.

At the heart of this study is the ever-fascinating question, "how do we heal from injury?". Carrie Adler and her team in the Department of Molecular Medicine are experts in leveraging planaria to understand stem cell behavior during regeneration. In this study the authors compare how stem cells respond to the loss of a specific organ versus the loss of several organs. At the heart of the discovery is that different types of injuries may require distinct regenerative mechanisms. In other words, planarian stem cells can tailor their behaviors based on the kind of healing that is needed.

Carrie Adler

Past Publications